Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1

ilustraciones, gráficas, tablas

Autores:: Vargas León, Carolina María

Tipo de recurso:

Fecha de publicación:: 2021

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

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network_acronym_str	UNACIONAL2
network_name_str	Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
dc.title.translated.eng.fl_str_mv	Identification and association of Toll-Like Receptor 3 polymorphisms with the development of mucosal Leishmaniasis against the coinfection Leishmania spp. - Leishmania RNA Virus 1
title	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
spellingShingle	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1 610 - Medicina y salud::616 - Enfermedades Leishmaniasis Receptor 3 Toll-Like Leishmania Leishmaniasis Toll-Like Receptor 3 Leishmania Leishmania LRV1 TLR3 Leishmaniasis mucosa Leishmaniasis cutánea Polimorfismo de nucleótido único Colombia rs3775296 rs764010322 rs3775291 rs3775290 Mucosal leishmaniasis Cutaneous leishmaniasis Single nucleotide polymorphism
title_short	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
title_full	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
title_fullStr	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
title_full_unstemmed	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
title_sort	Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1
dc.creator.fl_str_mv	Vargas León, Carolina María
dc.contributor.advisor.spa.fl_str_mv	Echeverry Gaitán, María Clara Cadavid Gutiérrez, Luis Fernando
dc.contributor.author.spa.fl_str_mv	Vargas León, Carolina María
dc.contributor.researchgroup.spa.fl_str_mv	Infecciones y Salud en El Trópico
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud::616 - Enfermedades
topic	610 - Medicina y salud::616 - Enfermedades Leishmaniasis Receptor 3 Toll-Like Leishmania Leishmaniasis Toll-Like Receptor 3 Leishmania Leishmania LRV1 TLR3 Leishmaniasis mucosa Leishmaniasis cutánea Polimorfismo de nucleótido único Colombia rs3775296 rs764010322 rs3775291 rs3775290 Mucosal leishmaniasis Cutaneous leishmaniasis Single nucleotide polymorphism
dc.subject.decs.spa.fl_str_mv	Leishmaniasis Receptor 3 Toll-Like Leishmania
dc.subject.decs.eng.fl_str_mv	Leishmaniasis Toll-Like Receptor 3 Leishmania
dc.subject.proposal.spa.fl_str_mv	Leishmania LRV1 TLR3 Leishmaniasis mucosa Leishmaniasis cutánea Polimorfismo de nucleótido único Colombia
dc.subject.proposal.none.fl_str_mv	rs3775296 rs764010322 rs3775291 rs3775290
dc.subject.proposal.eng.fl_str_mv	Mucosal leishmaniasis Cutaneous leishmaniasis Single nucleotide polymorphism
description	ilustraciones, gráficas, tablas
publishDate	2021
dc.date.issued.none.fl_str_mv	2021
dc.date.accessioned.none.fl_str_mv	2022-01-11T21:18:30Z
dc.date.available.none.fl_str_mv	2022-01-11T21:18:30Z
dc.type.spa.fl_str_mv	Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv	Text
dc.type.redcol.spa.fl_str_mv	http://purl.org/redcol/resource_type/TM
status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	https://repositorio.unal.edu.co/handle/unal/80802
dc.identifier.instname.spa.fl_str_mv	Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv	https://repositorio.unal.edu.co/
url	https://repositorio.unal.edu.co/handle/unal/80802 https://repositorio.unal.edu.co/
identifier_str_mv	Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv	spa
language	spa
dc.relation.indexed.spa.fl_str_mv	Bireme
dc.relation.references.spa.fl_str_mv	El-Bendary, M., Neamatallah, M., Elalfy, H., Besheer, T., Elkholi, A., El-Diasty, M., Elsareef, M., Zahran, M., El-Aarag, B., Gomaa, A., Elhammady, D., El-Setouhy, M., Hegazy, A., & Esmat, G. (2018). The association of single nucleotide polymorphisms of Toll-like receptor 3, Toll-like receptor 7 and Toll-like receptor 8 genes with the susceptibility to HCV infection. British Journal of Biomedical Science, 75(4), 175–181. https://doi.org/10.1080/09674845.2018.1492186 Engin, A., Arslan, S., Özbilüm, N., & Bakir, M. (2016). Is there any relationship between Toll-like receptor 3 c.1377C/T and −7C/A polymorphisms and susceptibility to Crimean Congo hemorrhagic fever? Journal of Medical Virology. https://doi.org/10.1002/jmv.24519 Eren, R. O., Reverte, M., Rossi, M., Hartley, M. A., Castiglioni, P., Prevel, F., Martin, R., Desponds, C., Lye, L. F., Drexler, S. K., Reith, W., Beverley, S. M., Ronet, C., & Fasel, N. (2016). Mammalian Innate Immune Response to a Leishmania-Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence. Cell Host and Microbe, 20(3), 318–328. https://doi.org/10.1016/j.chom.2016.08.001 Eshleman, E. M., Delgado, C., Kearney, S. J., Friedman, R. S., & Lenz, L. L. (2017). Down regulation of macrophage IFNGR1 exacerbates systemic L. monocytogenes infection. PLOS Pathogens, 13(5), e1006388. https://doi.org/10.1371/JOURNAL.PPAT.1006388 Fahey, T. J., Tracey, K. J., Tekamp-Olson, P., Cousens, L. S., Jones, W. G., Shires, G. T., Cerami, A., & Sherry, B. (1992). Macrophage inflammatory protein 1 modulates macrophage function. Journal of Immunology (Baltimore, Md. : 1950), 148(9), 2764–2769. http://www.ncbi.nlm.nih.gov/pubmed/1573267 Fairn, G. D., & Grinstein, S. (2012). How nascent phagosomes mature to become phagolysosomes. Trends in Immunology, 33(8), 397–405. https://doi.org/10.1016/j.it.2012.03.003 Fan, L., Zhou, P., Hong, Q., Chen, A.-X., Liu, G.-Y., Yu, K.-D., & Shao, Z.-M. (2019). Toll-like receptor 3 acts as a suppressor gene in breast cancer initiation and progression: a two-stage association study and functional investigation. https://doi.org/10.1080/2162402X.2019.1593801 Faraoni, I., Antonetti, F. R., Cardone, J., & Bonmassar, E. (2009). miR-155 gene: A typical multifunctional microRNA. In Biochimica et Biophysica Acta - Molecular Basis of Disease (Vol. 1792, Issue 6, pp. 497–505). Elsevier. https://doi.org/10.1016/j.bbadis.2009.02.013 Ferro, C., López, M., Fuya, P., Lugo, L., Manuel Cordovez, J., & González, C. (2015). Spatial Distribution of Sand Fly Vectors and Eco-Epidemiology of Cutaneous Leishmaniasis Transmission in Colombia. https://doi.org/10.1371/journal.pone.0139391 Filardy, A. A., Costa-Da-Silva, A. C., Koeller, C. M., Guimarães-Pinto, K., Ribeiro-Gomes, F. L., Lopes, M. F., Heise, N., Freire-De-Lima, C. G., Nunes, M. P., & DosReis, G. A. (2014). Infection with Leishmania major induces a cellular stress response in macrophages. PLoS ONE, 9(1). https://doi.org/10.1371/journal.pone.0085715 Fischer, J., Koukoulioti, E., Schott, E., Fülöp, B., Heyne, R., Berg, T., & Bömmel, F. van. (2018). Polymorphisms in the Toll-like receptor 3 ( TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population. Scientific Reports 2018 8:1, 8(1), 1–8. https://doi.org/10.1038/s41598-018-31065-6 Fox, J., & Bouchet-Valat, M. (2019). Rcmdr: R Commander. R package version 2.5-2. https://cran.r-project.org/web/packages/Rcmdr/Rcmdr.pdf Geng, P. L., Song, L. X., An, H., Huang, J. Y., Li, S., & Zeng, X. T. (2016). Toll-like receptor 3 is associated with the risk of HCV infection and HBV-related diseases. In Medicine (United States) (Vol. 95, Issue 21). Lippincott Williams and Wilkins. https://doi.org/10.1097/MD.0000000000002302 Mukherjee, Suprabhat, Huda, S., & Sinha Babu, S. P. (2019). Toll-like receptor polymorphism in host immune response to infectious diseases: A review. Scandinavian Journal of Immunology, 90(1), 1–18. https://doi.org/10.1111/sji.12771 Müller, K., Zandbergen, G., Hansen, B., Laufs, H., Jahnke, N., Solbach, W., & Laskay, T. (2001). Chemokines, natural killer cells and granulocytes in the early course of Leishmania major infection in mice. Medical Microbiology and Immunology, 190(1–2), 73–76. https://doi.org/10.1007/s004300100084 Muñoz, G., & Davies, C. R. (2006). Leishmania panamensis transmission in the domestic environment: the results of a prospective epidemiological survey in Santander, Colombia. Biomédica, 26, 131–144. https://doi.org/10.7705/BIOMEDICA.V26I1.1507 Murray, H. W. (2002). Kala-azar - Progress against a neglected disease. In New England Journal of Medicine (Vol. 347, Issue 22, pp. 1793–1794). https://doi.org/10.1056/NEJMe020133 Murray, R. K., Kennelly, P. J., Bender, D. A., Rodwell, V. W., Botham, K. M., & Weil, P. A. (2013). Harper, Bioquímica ilustrada (2da edició). McGraw Hill. Nahum, A., Dadi, H., Bates, A., & Roifman, C. M. (2011). The L412F variant of Toll-like receptor 3 (TLR3) is associated with cutaneous candidiasis, increased susceptibility to cytomegalovirus, and autoimmunity. Journal of Allergy and Clinical Immunology, 127(2), 528–531. https://doi.org/10.1016/j.jaci.2010.09.03 Nares, S., & Wahl, S. (2005). Monocytes and Macrophages. In Measuring Immunity: Basic Biology and Clinical Assessment (pp. 299–311). Academic Press. https://doi.org/10.1016/B978-012455900-4/50287-7 NCBI. (2018). ClinVar; [VCV000792634.2]. https://www.ncbi.nlm.nih.gov/clinvar/variation/792634/ NCBI. (2020). TLR3 toll like receptor 3 [ Homo sapiens (human) ] Gene ID: 7098. https://www.ncbi.nlm.nih.gov/gene/7098 Ogg, M. M., Carrion, R., Botelho, A. C. de C., Mayrink, W., Correa-Oliveira, R., & Patterson, J. L. (2003). Short report: quantification of leishmaniavirus RNA in clinical samples and its possible role in pathogenesis. The American Journal of Tropical Medicine and Hygiene, 69(3), 309–313. http://www.ncbi.nlm.nih.gov/pubmed/14628949 Okonechnikov, K., Golosova, O., & M, F. (2012). Unipro UGENE: a unified bioinformatics toolkit (38.1). Bioinformatics. https://doi.org/10.1093/bioinformatics/bts091 Olivier, M. (2011). Host-pathogen interaction: Culprit within a culprit. Nature, 471(7337), 173–174. https://doi.org/10.1038/471173a Organización Panamericana de la Salud. (2020). Leishmaniasis: Informe epidemiológico de las Américas. Núm. 9, diciembre del 2020. (Vol. 9). https://iris.paho.org/handle/10665.2/51742 Ovalle-Bracho, C., Camargo, C., Díaz-Toro, Y., & Parra-Muñoz, M. (2018). Molecular typing of Leishmania (Leishmania) amazonensis and species of the subgenus Viannia associated with cutaneous and mucosal leishmaniasis in Colombia: A concordance study. Biomédica, 38(1), 86–95. https://doi.org/10.7705/BIOMEDICA.V38I0.3632 Parra-Muñoz, M., Aponte, S., Ovalle-Bracho, C., Saavedra, C., & Echeverry, M. C. (2021). Detection of Leishmania RNA Virus in Clinical Samples from Cutaneous Leishmaniasis Patients Varies according to the Type of Sample. The American Journal of Tropical Medicine and Hygiene, 104(1), 233–239. https://doi.org/10.4269/ajtmh.20-0073 Pauwels, A. M., Trost, M., Beyaert, R., & Hoffmann, E. (2017). Patterns, Receptors, and Signals: Regulation of Phagosome Maturation. In Trends in Immunology (Vol. 38, Issue 6, pp. 407–422). Elsevier Ltd. https://doi.org/10.1016/j.it.2017.03.006 Pazmiño, Fredy A., Parra-Muñoz, M., Saavedra, C. H., Muvdi-Arenas, S., Ovalle-Bracho, C., & Echeverry, M. C. (2021). Leishmania RNA virus is associated with the occurrence of mucosal leishmaniasis caused by species from the Leishmania Viannia subgenus. [Artículo Sometido Para Publicación En American Journal of Tropical Medicine & Hygiene]. Pazmiño, Fredy Alexander. (2020). Determinación de la asociación entre la presencia del Leishmaniavirus 1 (LRV-1) en parásitos infectantes de Leishmania spp y el desarrollo de la leishmaniasis mucosa en pacientes diagnosticados de leishmaniasis cutánea en Colombia. Universidad Nacional de Colombia. Perry, K., & Agabian, N. (1991). mRNA processing in the Trypanosomatidae. In Experientia (Vol. 47, Issue 2, pp. 118–128). Birkhäuser-Verlag. https://doi.org/10.1007/BF01945412 Phan, L., Jin, Y., Zhang, H., Qiang, W., Shekhtman, E., Shao, D., Revoe, ., Villamarin, R., Ivanchenko, E., Kimura, M., Wang, Z. Y., Hao, L., Sharopova, N., Bihan, M., Sturcke, A., Lee, M., Popova, N., Wu, W., Bastiani, C., … Kattman, B. L. (2020). “ALFA: Allele Frequency Aggregator.” National Center for Biotechnology Information, U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/snp/docs/gsr/alfa/ Poirier, V., & Av-Gay, Y. (2015). Intracellular Growth of Bacterial Pathogens: The Role of Secreted Effector Proteins in the Control of Phagocytosed Microorganisms. Microbiology Spectrum, 3(6). https://doi.org/10.1128/microbiolspec.vmbf-0003-2014 Qi, R., Hoose, S., Schreiter, J., Sawant, K. V, Lamb, R., Ranjith-Kumar, C. T., Mills, J., San Mateo, L., Jordan, J. L., & Cheng Kao, C. (2010). Secretion of the Human Toll-like Receptor 3 Ectodomain Is Affected by Single Nucleotide Polymorphisms and Regulated by Unc93b1. The Journal of Biological Chemistry, 285(47), 36635–36644. https://doi.org/10.1074/jbc.M110.144402 Raes, G., Beschin, A., Ghassabeh, G. H., & De Baetselier, P. (2007). Alternatively activated macrophages in protozoan infections. Current Opinion in Immunology, 19(4), 454–459. https://doi.org/10.1016/j.coi.2007.05.007 Ranjith-Kumar, C. T., Miller, W., Sun, J., Xiong, J., Santos, J., Yarbrough, I., Lamb, R. J., Mills, J., Duffy, K. E., Hoose, S., Cunningham, M., Holzenburg, A., Mbow, M. L., Sarisky, R. T., & Kao, C. C. (2007). Effects of single nucleotide polymorphisms on toll-like receptor 3 activity and expression in cultured cells. Journal of Biological Chemistry, 282(24), 17696–17705. https://doi.org/10.1074/jbc.M700209200 Rayamajhi, M., Humann, J., Penheiter, K., Andreasen, K., & Lenz, L. L. (2010). Induction of IFN-αβ enables Listeria monocytogenes to suppress macrophage activation by IFN-γ. The Journal of Experimental Medicine, 207(2), 327. https://doi.org/10.1084/JEM.20091746 Rodríguez, G., Arenas, C., Ovalle, C., Hernández, C. A., & Camargo, C. (2016). La Leishmaniasis: Atllas y texto (C. A. Hernández (ed.)). Hospital Universitario Centro Dermatológico Federico Lleras Acosta, E.S.E. Rogers, L. (1904). PRELIMINARY NOTE ON THE DEVELOPMENT OF TRYPANOSOMA IN CULTURES OF THE CUNNINGHAM-LEISHMAN-DONOVAN BODIES OF CACHEXIAL FEVER AND KALA-AZAR. The Lancet, 164(4221), 215–216. https://doi.org/10.1016/S0140-6736(01)03458-4 Rogers, L. (1906). Further work on the development of the hepatomonas of Kala-Azar and cachexial fever from Leishman-Donovan bodies. Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character, 77(517), 284–293. https://doi.org/10.1098/rspb.1906.0017 Ross, M. R. (1903). Further notes on leishman’s bodies. British Medical Journal, 2(2239), 1401. https://doi.org/10.1136/bmj.2.2239.1401 Rossi, M., Castiglioni, P., Hartley, M. A., Eren, R. O., Prével, F., Desponds, C., Utzschneider, D. T., Zehn, D., Cusi, M. G., Kuhlmann, F. M., Beverley, S. M., Ronet, C., & Fasel, N. (2017). Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis. Proceedings of the National Academy of Sciences of the United States of America, 114(19), 4987–4992. https://doi.org/10.1073/pnas.1621447114 Rossi, M., & Fasel, N. (2018). How to master the host immune system? Leishmania parasites have the solutions! International Immunology, 30(3), 103–111. https://doi.org/10.1093/INTIMM/DXX075 Saiz, M., Llanos-Cuentas, A., Echevarria, J., Roncal, N., Cruz, M., Muniz, M. T., Lucas, C., Wirth, D. F., Scheffter, S., Magill, A. J., & Patterson, J. L. (1998). SHORT REPORT: DETECTION OF LEISHMANIAVIRUS IN HUMAN BIOPSY SAMPLES OF LEISHMANIASIS FROM PERU. In Am. J. Trop. Med. Hyg (Vol. 58, Issue 2). Santos, C. N. O., Ribeiro, D. R., Cardoso Alves, J., Cazzaniga, R. A., Magalhães, L. S., De Souza, M. S. F., Fonseca, A. B. L., Bispo, A. J. B., Porto, R. L. S., Santos, C. A. Dos, Da Silva, Â. M., Teixeira, M. M., De Almeida, R. P., & De Jesus, A. R. (2019). Association between Zika Virus Microcephaly in Newborns with the rs3775291 Variant in Toll-Like Receptor 3 and rs1799964 Variant at Tumor Necrosis Factor-α Gene. Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiz392 Sassi, A., Louzir, H., Ben Salah, A., Mokni, M., Ben Osman, A., & Dellagi, K. (1999). Leishmanin skin test lymphoproliferative responses and cytokine production after symptomatic or asymptomatic Leishmania major infection in Tunisia. Clinical and Experimental Immunology, 116(1), 127–132. https://doi.org/10.1046/j.1365-2249.1999.00844.x Scheffter, S. M., Ro, Y. T., Chung, I. K., & Patterson, J. L. (1995). The Complete Sequence of Leishmania RNA Virus LRV2-1, a Virus of an Old World Parasite Strain. Virology, 212(1), 84–90. https://doi.org/10.1006/viro.1995.1456 Scheffter, S., Widmer, G., & Patterson, J. L. (1994). Complete Sequence of Leishmania RNA Virus 1-4 and Identification of Conserved Sequences. Virology, 199(2), 479–483. https://doi.org/10.1006/viro.1994.1149 Schröder, N. W. J., & Schumann, R. R. (2005). Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. In Lancet Infectious Diseases (Vol. 5, Issue 3, pp. 156–164). Lancet Publishing Group. https://doi.org/10.1016/S1473-3099(05)01308-3 Sghaier, I., Zidi, S., Mouelhi, L., Ghazoueni, E., Brochot, E., Almawi, W. Y., & Loueslati, B. Y. (2019). TLR3 and TLR4 SNP variants in the liver disease resulting from hepatitis B virus and hepatitis C virus infection. British Journal of Biomedical Science, 76(1), 35–41. https://doi.org/10.1080/09674845.2018.1547179 Sironi, M., Biasin, M., Cagliani, R., Forni, D., De Luca, M., Saulle, I., Lo Caputo, S., Mazzotta, F., Macías, J., Pineda, J., Caruz, A., & Clerici, M. (2012). Natural Resistance to HIV-1 Infection Confers TLR3 A Common Polymorphism in. The Journal of Immunology, 188(2), 818–823. https://doi.org/10.4049/jimmunol.1102179 Software MacKiev. (2021). GraphPad Prism (9.1.2). www.graphpad.com Song, G., Ouyang, G., & Bao, S. (2005). The activation of Akt/PKB signaling pathway and cell survival. In Journal of Cellular and Molecular Medicine (Vol. 9, Issue 1, pp. 59–71). Journal of Cellular and Molecular Medicine. https://doi.org/10.1111/j.1582-4934.2005.tb00337.x Song, G., Ouyang, G., & Bao, S. (2005). The activation of Akt/PKB signaling pathway and cell survival. In Journal of Cellular and Molecular Medicine (Vol. 9, Issue 1, pp. 59–71). Journal of Cellular and Molecular Medicine. https://doi.org/10.1111/j.1582-4934.2005.tb00337.x Song, G., Ouyang, G., & Bao, S. (2005). The activation of Akt/PKB signaling pathway and cell survival. In Journal of Cellular and Molecular Medicine (Vol. 9, Issue 1, pp. 59–71). Journal of Cellular and Molecular Medicine. https://doi.org/10.1111/j.1582-4934.2005.tb00337.x Stuart, K. D., Weeks, R., Guilbride, L., & Myler, P. J. (1992). Molecular organization of Leishmania RNA virus 1. Proceedings of the National Academy of Sciences of the United States of America, 89(18), 8596–8600. https://doi.org/10.1073/pnas.89.18.8596 Studzińska, M., Jabłońska, A., Wiśniewska-Ligier, M., Nowakowska, D., Gaj, Z., Leśnikowski, Z. J., Woźniakowska-Gęsicka, T., Wilczyński, J., & Paradowska, E. (2017). Association of TLR3 L412F Polymorphism with Cytomegalovirus Infection in Children. https://doi.org/10.1371/journal.pone.0169420 Svensson, A., Tunbäck, P., Nordström, I., Padyukov, L., & Eriksson, K. (2012). Polymorphisms in Toll-like receptor 3 confer natural resistance to human herpes simplex virus type 2 infection. Journal of General Virology. https://doi.org/10.1099/vir.0.042572-0 Tarr, P. I., Aline, R. F., Smiley, B. L., Scholler, J., Keithly, J., & Stuart, K. (1988). LR1: A candidate RNA virus of Leishmania. Proceedings of the National Academy of Sciences of the United States of America, 85(24), 9572–9275. https://doi.org/10.1073/pnas.85.24.9572 Telleria, E. L., Martins-Da-Silva, A., Tempone, A. J., & Traub-Cseko, Y. M. (2018). Leishmania, microbiota and sand fly immunity. Parasitology, 145(10), 1336–1353. https://doi.org/10.1017/S0031182018001014 Tripathi, P., Singh, V., & Naik, S. (2007). Immune response to leishmania: Paradox rather than paradigm. FEMS Immunology and Medical Microbiology, 51(2), 229–242. https://doi.org/10.1111/j.1574-695X.2007.00311.x Ueno, N., & Wilson, M. E. (2012). Receptor-mediated phagocytosis of Leishmania: Implications for intracellular survival. Trends in Parasitology, 28(8), 335–344. https://doi.org/10.1016/j.pt.2012.05.002 Ullah, M. O., Sweet, M. J., Mansell, A., Kellie, S., & Kobe, B. (2016). TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target. Journal of Leukocyte Biology. https://doi.org/10.1189/jlb.2ri1115-531r Ullah, M. O., Ve, T., Mangan, M., Alaidarous, M., Sweet, M. J., Mansell, A., & Kobe, B. (2013). The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain with structural similarity to IFIT proteins. Biological Crystallography , 69, 2420–2430. https://doi.org/10.1107/S0907444913022385 UniProt. (n.d.). UniProtKB - O15455 (TLR3_HUMAN). Retrieved May 20, 2021, from https://www.uniprot.org/uniprot/O15455 van Griensven, J., & Diro, E. (2012). Visceral Leishmaniasis. In Infectious Disease Clinics of North America (Vol. 26, Issue 2, pp. 309–322). Elsevier. https://doi.org/10.1016/j.idc.2012.03.005 Vargas Córdoba, M. (2016). Virología médica (2da ed.). Universidad Nacional de Colombia y Manual Moderno. von Stebut, E., & Tenzer, S. (2018). Cutaneous leishmaniasis: Distinct functions of dendritic cells and macrophages in the interaction of the host immune system with Leishmania major. International Journal of Medical Microbiology, 308(1), 206–214. https://doi.org/10.1016/j.ijmm.2017.11.002 Wang, B. G., Yi, D. H., & Liu, Y. F. (2015). TLR3 gene polymorphisms in cancer: A systematic review and meta-analysis. Chinese Journal of Cancer, 34(6). https://doi.org/10.1186/s40880-015-0020-z Wang, Y., Liu, L., Davies, D. R., & Segal, D. M. (2010). Dimerization of Toll-like Receptor 3 (TLR3) Is Required for Ligand Binding. The Journal of Biological Chemistry, 285(47), 36836. https://doi.org/10.1074/JBC.M110.16797 Weeks, R., Aline, R. F., Myler, P. J., & Stuart, K. (1992). LRV1 viral particles in Leishmania guyanensis contain double-stranded or single-stranded RNA. Journal of Virology, 66(3), 1389–1393. https://doi.org/10.1128/jvi.66.3.1389-1393.1992 WHO. (2019). Leishmaniasis - Number of cases of cutaneus leishmaniasis: 2018. https://apps.who.int/neglected_diseases/ntddata/leishmaniasis/leishmaniasis.html WHO. (2021). Leishmaniasis. https://www.who.int/news-room/fact-sheets/detail/leishmaniasis Widmer, G., Comeau, A. M., Furlong, D. B., Wirth, D. F., & Patterson, J. L. (1989). Characterization of a RNA virus from the parasite Leishmania. Proceedings of the National Academy of Sciences of the United States of America, 86(15), 5979–5982. https://doi.org/10.1073/pnas.86.15.5979 Widmer, G., & Dooley, S. (1995). Phylogenetic analysis of Leishmania RNA virus and Leishmania suggests ancient virus-p3arasite association. In rNucleic Acids Research (Vol. 23, Issue 12). Xia, D., Ye, S., Zhang, X., bao Zhang, Y., Tian, X., Liu, A., Cui, C., & Shi, L. (2020). Association of TLR3 (rs3775291) and IL-10 (rs1800871) gene polymorphisms with susceptibility to Hepatitis B infection: A meta-analysis. Epidemiology and Infection, 148, 1–11. https://doi.org/10.1017/S0950268820002101 Yang, C. A., Raftery, M. J., Hamann, L., Guerreiro, M., Grütz, G., Haase, D., Unterwalder, N., Schönrich, G., Schumann, R. R., Volk, H. D., & Scheibenbogen, C. (2012). Association of TLR3-hyporesponsiveness and functional TLR3 L412F polymorphism with recurrent herpes labialis. Human Immunology, 73(8), 844–851. https://doi.org/10.1016/j.humimm.2012.04.008 Ye, N., Ding, Y., Wild, C., Shen, Q., & Zhou, J. (2014). Small molecule inhibitors targeting activator protein 1 (AP-1). Journal of Medicinal Chemistry, 57(16), 6930–6948. https://doi.org/10.1021/JM5004733 Zayed, R. A., Omran, D., Mokhtar, D. A., Zakaria, Z., Ezzat, S., Soliman, M. A., Mobarak, L., El-Sweesy, H., & Emam, G. (2017). Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients. Am. J. Trop. Med. Hyg, 96(3), 720–726. https://doi.org/10.4269/ajtmh.16-0644 Zhou, P., Fan, L., Yu, K.-D., Zhao, M.-W., & Li, X.-X. (2011). Toll-like receptor 3 C1234T may protect against geographic atrophy through decreased dsRNA binding capacity. The FASEB Journal, 25(10), 3489–3495. https://doi.org/10.1096/FJ.11-189258 Zilberstein, & Dwyer. (1988). Identification of a surface membrane proton-translocating ATPase in promastigotes of the parasitic protozoan Leishmania donovani. Biochemical Journal, 256(1), 13–21. https://doi.org/10.1042/bj2560013 Zilberstein, Philosoph, & Gepstein. (1989). Maintenance of cytoplasmic pH and proton motive force in promastigotes of Leishmania donovani. Molecular and Biochemical Parasitology, 36(2), 109–117. https://doi.org/10.1016/0166-6851(89)90183-7 Abbas, A., Litchtman, A., & Pillai, S. (2015). Inmunología celular y molecular. In El Sevier (8va ed.). Agudelo Chivatá, N. J. (2019a). Informe de evento: Leishmaniasis cutánea. Agudelo Chivatá, N. J. (2019b). Informe de evento: Leishmaniasis mucosa. Agudelo, S., & Robledo, S. (2000). Revisión de tema: respuesta inmune en infecciones humanas por Leishmania spp. Iatreia, 13(3), 167–178 Akashi-Takamura, S., & Miyake, K. (2006). Toll-like receptors (TLRs) and immune disorders. In Journal of Infection and Chemotherapy (Vol. 12, Issue 5, pp. 233–240). Springer Japan. https://doi.org/10.1007/s10156-006-0477-4 Alagarasu, K., Bachal, R. V., Memane, R. S., Shah, P. S., & Cecilia, D. (2015). Polymorphisms in RNA sensing toll like receptor genes and its association with clinical outcomes of dengue virus infection. Immunobiology, 220(1), 164–168. https://doi.org/10.1016/J.IMBIO.2014.09.020 Alcolea, P. J., Alonso, A., Gómez, M. J., Postigo, M., Molina, R., Jiménez, M., & Larraga, V. (2014). Stage-specific differential gene expression in Leishmania infantum: From the foregut of Phlebotomus perniciosus to the human phagocyte. BMC Genomics, 15(1). https://doi.org/10.1186/1471-2164-15-849 Alexander, J., & Russell, D. G. (1992). The Interaction of Leishmania Species with Macrophages. Advances in Parasitology, 31(C), 175–254. https://doi.org/10.1016/S0065-308X(08)60022-6 Alipoor, B., Ghaedi, H., Davood Omrani, M., Bastami, M., Meshkani, R., & Golmohammadi, T. (2016). A Bioinformatics Approach to Prioritize Single Nucleotide Polymorphisms in TLRs Signaling Pathway Genes. Internationa Journal of Molecular and Celular Medicine, 5(2). http://compbio.uthsc.edu/miRSNP/ Arbour, N. C., Lorenz, E., Schutte, B. C., Zabner, J., Kline, J. N., Jones, M., Frees, K., Watt, J. L., & Schwartz, D. A. (2000). TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nature Genetics, 25(2), 187–191. https://doi.org/10.1038/76048 Aronson, N., Herwaldt, B. L., Libman, M., Pearson, R., Lopez-Velez, R., Weina, P., Carvalho, E., Ephros, M., Jeronimo, S., & Magill, A. (2017). Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). The American Journal of Tropical Medicine and Hygiene, 96(1), 24. https://doi.org/10.4269/AJTMH.16-84256 Atayde, V. D., da Silva Lira Filho, A., Chaparro, V., Zimmermann, A., Martel, C., Jaramillo, M., & Olivier, M. (2019). Exploitation of the Leishmania exosomal pathway by Leishmania RNA virus 1. Nature Microbiology, 4(4), 714–723. https://doi.org/10.1038/s41564-018-0352-y Atsaves, V., Leventaki, V., Rassidakis, G. Z., & Claret, F. X. (2019). AP-1 Transcription Factors as Regulators of Immune Responses in Cancer. Cancers, 11(7). https://doi.org/10.3390/CANCERS11071037 Avendaño-Tamayo, E., Rúa, A., Parra-Marín, M. V., Rojas, W., Campo, O., Chacón-Duque, J., Agudelo-Flórez, P., Narváez, C. F., Salgado, D. M., Restrepo, B. N., & Bedoya, G. (2019). Evaluation of variants in IL6R, TLR3, and DC-SIGN genes associated with dengue in a sampled Colombian population. Biomedica, 39(1), 88–101. https://doi.org/10.7705/biomedica.v39i1.4029 Awasthi, A., Mathur, R. K., & Saha, B. (2004). Immune response to Leishmania infection. Indian Journal of Medical Research, 119(6), 238–258. Azambuja, P., Garcia, E. S., & Ratcliffe, N. A. (2005). Gut microbiota and parasite transmission by insect vectors. Trends in Parasitology, 21(12), 568–572. https://doi.org/10.1016/j.pt.2005.09.011 Bailey, M. S., & Lockwood, D. N. J. (2007). Cutaneous leishmaniasis. Clinics in Dermatology, 25(2), 203–211. https://doi.org/10.1016/j.clindermatol.2006.05.008 Bañuls, A. L., Hide, M., & Prugnolle, F. (2007). Leishmania and the Leishmaniases: A Parasite Genetic Update and Advances in Taxonomy, Epidemiology and Pathogenicity in Humans. Advances in Parasitology, 64, 1–109. https://doi.org/10.1016/S0065-308X(06)64001-3 Bell, J. K., Botos, I., Hall, P. R., Askins, J., Shiloach, J., Davies, D. R., & Segal, D. M. (2006). The molecular structure of the TLR3 extracellular domain. Journal of Endotoxin Research, 12(6), 375–378. https://doi.org/10.1177/09680519060120060801 Bogdan, C., & Röllinghoff, M. (1998). The immune response to Leishmania: Mechanisms of parasite control and evasion. International Journal for Parasitology, 28(1), 121–134. https://doi.org/10.1016/S0020-7519(97)00169-0 Bruschi, F., & Gradoni, L. (2018). The leishmaniases: Old neglected tropical diseases. In The Leishmaniases: Old Neglected Tropical Diseases. Springer International Publishing. https://doi.org/10.1007/978-3-319-72386-0 Cadd, T. L., Keenan, M. C., & Pattersonl, J. L. (1993). Detection of Leishmania RNA Virus 1 Proteins. In JOURNAL OF VIROLOGY. http://jvi.asm.org/ Cantanhêde, L. M., da Silva Júnior, C. F., Ito, M. M., Felipin, K. P., Nicolete, R., Salcedo, J. M. V., Porrozzi, R., Cupolillo, E., & Ferreira, R. de G. M. (2015). Further Evidence of an Association between the Presence of Leishmania RNA Virus 1 and the Mucosal Manifestations in Tegumentary Leishmaniasis Patients. PLOS Neglected Tropical Diseases, 9(9), e0004079. https://doi.org/10.1371/journal.pntd.0004079 CDC. (n.d.). CDC - Leishmaniasis - Biology. Retrieved February 27, 2020, from https://www.cdc.gov/parasites/leishmaniasis/biology.html Centers for disease control and prevention (CDC). (2020, February 14). CDC - Leishmaniasis. https://www.cdc.gov/parasites/leishmaniasis/index.html Chattopadhyay, S., & Sen, G. C. (2014). dsRNA-Activation of TLR3 and RLR Signaling: Gene Induction-Dependent and Independent Effects. Journal of Interferon & Cytokine Research, 34(6), 436. https://doi.org/10.1089/JIR.2014.0034 Chaudhuri, G., Chaudhuri, M., Pan, A., & Chang, K.-P. (1989). Surface Acid Proteinase (gp63) of Leishmania mexicana. The Journal of Biological Chemestry, 264(13), 7483–7489. Chen, B., Cole, J. W., & Grond-Ginsbach, C. (2017). Departure from Hardy Weinberg Equilibrium and Genotyping Error. Frontiers in Genetics, 8(OCT), 167. https://doi.org/10.3389/FGENE.2017.00167 Chieco, P., & Derenzini, M. (1999). The Feulgen reaction 75 years on. Histochemistry and Cell Biology, 111(5), 345–358. https://doi.org/10.1007/s004180050367 Choe, J., Kelker, M. S., & Wilson, I. A. (2005). Crystal Structure of Human Toll-Like Receptor 3 (TLR3) Ectodomain. Science, 309(5734), 581–585. https://doi.org/10.1126/science.1115253 Coombs, G., & North, M. (2004). Biochemical Protozoology. In Journal of Chemical Information and Modeling. Taylor & Francis. https://doi.org/10.1017/CBO9781107415324.004 Corthay, A. (2006). A three-cell model for activation of naïve T helper cells. Scandinavian Journal of Immunology, 64(2), 93–96. https://doi.org/10.1111/j.1365-3083.2006.01782.x Croft, S. L., & Molyneux, D. H. (1979). Studies on the ultrastructure, virus-like particles and infectivity of Leishmania hertigi. Annals of Tropical Medicine and Parasitology, 73(3), 213–226. https://doi.org/10.1080/00034983.1979.11687251 Cruz-Barrera, M. L., Ovalle-Bracho, C., Ortegon-Vergara, V., Pérez-Franco, J. E., & Echeverry, M. C. (2015). Improving Leishmania species identification in different types of samples from cutaneous lesions. Journal of Clinical Microbiology, 53(4), 1339–1341. https://doi.org/10.1128/JCM.02955-14 David, C. V., & Craft, N. (2009). Cutaneous and mucocutaneous leishmaniasis. Dermatologic Therapy, 22(6), 491–502. https://doi.org/10.1111/j.1529-8019.2009.01272.x de Carvalho, R. V. H., Andrade, W. A., Lima-Junior, D. S., Dilucca, M., de Oliveira, C. V., Wang, K., Nogueira, P. M., Rugani, J. N., Soares, R. P., Beverley, S. M., Shao, F., & Zamboni, D. S. (2019). Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome. Cell Reports, 26(2), 429-437.e5. https://doi.org/10.1016/J.CELREP.2018.12.047 de Carvalho, R. V. H., Lima-Junior, D. S., da Silva, M. V. G., Dilucca, M., Rodrigues, T. S., Horta, C. V., Silva, A. L. N., da Silva, P. F., Frantz, F. G., Lorenzon, L. B., Souza, M. M., Almeida, F., Cantanhêde, L. M., Ferreira, R. de G. M., Cruz, A. K., & Zamboni, D. S. (2019). Leishmania RNA virus exacerbates Leishmaniasis by subverting innate immunity via TLR3-mediated NLRP3 inflammasome inhibition. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-13356-2 de Carvalho, R. V. H., Lima-Júnior, D. S., de Oliveira, C. V., & Zamboni, D. S. (2021). Endosymbiotic RNA virus inhibits Leishmania-induced caspase-11 activation. IScience, 24(1), 102004. https://doi.org/10.1016/J.ISCI.2020.102004 de Souza, M. M., Manzine, L. R., da Silva, M. V. G., Bettini, J., Portugal, R. V., Cruz, A. K., Arruda, E., & Thiemann, O. H. (2014). An improved purification procedure for Leishmania RNA virus (LRV). Brazilian Journal of Microbiology, 45(2), 695–698. https://doi.org/10.1590/S1517-83822014000200044 Deeba, E., Koptides, D., Lambrianides, A., Pantzaris, M., Krashias, G., & Christodoulou, C. (2019). Complete sequence analysis of human toll-like receptor 3 gene in natural killer cells of multiple sclerosis patients. Multiple Sclerosis and Related Disorders, 33(May), 100–106. https://doi.org/10.1016/j.msard.2019.05.027 Dermine, J.-F., Duclos, S., rome Garin, J., ois St-Louis, F., Rea, S., Parton, R. G., & Desjardins, M. (2001). Flotillin-1-enriched Lipid Raft Domains Accumulate on Maturing Phagosomes* Downloaded from. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 276(21), 18507–18512. https://doi.org/10.1074/jbc.M101113200 Dowlati, Y. (1996). Cutaneous leishmaniasis: Clinical aspect. Clinics in Dermatology, 14(5), 425–431. https://doi.org/10.1016/0738-081X(96)00058-2 Dutta, S. K., & Tripathi, A. (2017). Association of toll-like receptor polymorphisms with susceptibility to chikungunya virus infection. Virology. https://doi.org/10.1016/j.virol.2017.08.009 Ehrchen, J. M., Roebrock, K., Foell, D., Nippe, N., von Stebut, E., Weiss, J. M., Münck, N. A., Viemann, D., Varga, G., Müller-Tidow, C., Schuberth, H. J., Roth, J., & Sunderkötter, C. (2010). Keratinocytes determine Th1 immunity during early experimental leishmaniasis. PLoS Pathogens, 6(4), 1–16. https://doi.org/10.1371/journal.ppat.1000871
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dc.publisher.spa.fl_str_mv	Universidad Nacional de Colombia
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dc.publisher.faculty.spa.fl_str_mv	Facultad de Medicina
dc.publisher.place.spa.fl_str_mv	Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv	Universidad Nacional de Colombia - Sede Bogotá
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spelling	Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Echeverry Gaitán, María Clarae040dbadd72121efdf7220643864e808Cadavid Gutiérrez, Luis Fernando3e6f3be0eb3276e983569e7157676dbbVargas León, Carolina María2d251fe2bebfdc40c56f3249abcd701a600Infecciones y Salud en El Trópico2022-01-11T21:18:30Z2022-01-11T21:18:30Z2021https://repositorio.unal.edu.co/handle/unal/80802Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, gráficas, tablasLa leishmaniasis es una enfermedad de transmisión vectorial producida por parásitos del género Leishmania. Esta enfermedad presenta tres manifestaciones clínicas: Leishmaniasis cutánea (LC), Leishmaniasis mucosa (LM) y Leishmaniasis visceral. LC se caracteriza por la aparición de pápulas y úlceras en la piel, mientras LM está dada por la aparición de úlceras en la cavidad oral o nasofaríngea; LM suele estar antecedida por LC, por lo que algunos autores consideran la LM como una progresión o complicación de la enfermedad. Si bien las razones por las cuales se produce LM aún no son del todo claras, se ha evidenciado que la presencia de Leishmania RNA Virus 1 (LRV1) en la cepa infectante de Leishmania se asocia con el desarrollo de LM, se ha planteado que el reconocimiento de LRV1 por el receptor de reconocimiento de patrones (PRR) endosomal Toll-like receptor 3 (TLR3) induce la activación de una respuesta inmune antiviral que favorece la persistencia y diseminación del parásito en el hospedero. El gen que codifica para TLR3 presenta varios polimorfismos de único nucleótido (SNPs) que se han visto asociados a resistencia o susceptibilidad frente a diversas infecciones virales. La presente investigación evaluó si los SNPs de TLR3 en población colombiana se asocian con el desarrollo de LM, ya sea en contexto de infección simple por Leishmania spp. o en coinfección Leishmania spp. – LRV1. Se efectuó un estudio retrospectivo de casos y controles, en donde se genotipificaron los exones 2, 3 y 4 del gen TLR3. Se analizó la presencia de polimorfismos en este grupo de exones en una población colombiana compuesta por 60 controles (muestras de pacientes diagnosticados con LC y sin complicación mucosa) y 27 casos (muestras de pacientes diagnosticados con LM) y mediante comparación de las frecuencias alélicas y genotípicas en cada grupo se evaluó la potencial asociación entre los SNPs y el desenlace clínico de la enfermedad. Adicionalmente, se evaluaron otras variables que pudiesen asociarse con el desarrollo de LM como lo son: sexo, edad, tratamiento, entre otras, y se evaluó la estructura génica de TLR3 en la población colombiana; para esta última, se contrastó con la estructura génica de otras poblaciones a nivel mundial como población europea, asiática y africana, además de analizar su comportamiento en un contexto local, al contrastar los resultados obtenidos con población latinoamericana. Se observaron cuatro polimorfismos en la muestra de estudio, un SNP en el exón 2 del gen, en la región codificante para 5’UTR (rs3775296), y tres SNPs en el exón 4: dos mutaciones sinónimas (rs764010322 y rs3775290) y una mutación no sinónima (rs3775291) que induce la variación L412F en la proteína. No se encontró ninguna asociación entre estos cuatro SNPs y el desarrollo de LM al evaluarlo en contexto de infección simple ni en coinfección. Tras analizar la estructura poblacional de la muestra colombiana aquí estudiada, se encontró que el comportamiento de rs3775296, en el exón 2, y rs3775291, en el exón 4, es muy similar a lo reportado en otras poblaciones a nivel mundial (p>0,05). Por el contrario, la distribución de frecuencias de los polimorfismos rs764010322 y rs3775291 del exón 4, si evidenció diferencias significativas frente a otras poblaciones (p<0,001). Estas diferencias están dadas porque, para la variación rs764010322, se evidenció una mayor frecuencia de aparición de ésta variación en la muestra de estudio que en otras poblaciones a nivel global y para rs3775291, se presentó la ausencia de uno de los tres alelos posibles que se han reportado para esta variación. Finalmente, se analizaron otras variables que pudieran estar asociadas con el desarrollo de la LM y se ratificó la asociación entre está y la presencia de LRV1+ y con la variable tratamiento para LC. (Texto tomado de la fuente).Leishmaniasis is a vector-borne disease produced by Leishmania parasites with three main clinical forms of the disease, cutaneous (CL), mucosal (ML), and visceral Leishmaniasis. CL causes skin lesions, papules, and ulcers, while ML causes ulcerative lesions on nasal and oropharyngeal mucosa. Usually, ML is preceded by CL, and some authors refer to it as a metastatic progression of the disease. The causes of ML remain unknown, although the presence of Leishmania RNA virus 1 (LRV1) in the parasite has been associated with the development of ML. Indeed, it has been suggested that the recognition of LRV1 by the endosomal pattern recognition receptor (PRR) TLR3 induces an antiviral response that allows the parasite’s persistence and dissemination in the host. TLR3 gene has several single nucleotide polymorphisms (SNPs) associated with resistance or susceptibility to viral infectious diseases. This work evaluated whether TLR3 SNPs are associated with ML development in infection produced by Leishmania spp. or Leishmania spp-LRV1 co-infection. The study was designed as a case-control study and TLR3 exons 2, 3, and 4 were genotyped. The presence of SNPs on TLR3 was analyzed in a Colombian population of 60 controls (CL diagnosed patients without mucosal compromise) and 27 cases (ML diagnosed patients) and the potential association between the SNPs and the clinical outcome were evaluated by comparing the allelic and genotypic frequencies for those SNPs. Other variables that could be associated with ML were also evaluated: sex, age, and treatment, among others; the genetic structure of TLR3 in the Colombian population in the context of other populations genotypes and haplotypes such as European, African, Asian, and Latin-American. Four SNPs were found between the studied sample: one exon 2, in the 5’UTR region (rs3775296), and three on exon 4 [two synonym mutations (rs764010322 y rs3775290) and one non-synonym mutation (rs3775291) that produced the L412F change in the protein]. There was no association observed between the found SNPs and the development of ML. The genetic population structure shows that rs3775296, on exon 2, and rs3775291, on exon 4, had a similar frequency to the world populations analyzed (p>0,05) while rs764010322 and rs3775291 had a significantly different frequency to world populations (p<0,001). Those differences are due to a higher frequency of rs764010322 variation and to the absence of one of the three possible alleles reported to rs3775291 into the studied population. Finally, other variables associated with the clinical development of the disease were analyzed and the association between LRV1presence and ML development was confirmed as the potential association between absent or incomplete treatment for CL event and ML appearance.Incluye anexosMaestríaMagíster en InmunologíaLa presente investigación es un estudio de asociación genotípica, definido como un estudio descriptivo, retrospectivo de casos y controles. Para el desarrollo de este estudio se genotificó el gen TLR3 de muestra provenientes de pacientes diagnosticados con Leishmaniasis cutánea (controles) y Leishmaniasis mucosa (casos). Tras la secuenciación se identificaron SNPs de dicho gen y se efectuaron análisis de asociación a partir de la frecuencias genotípicas y alélicas evidenciadas. Adicionalmente efectuó una comparación entre el comportamiento de TLR3 en la población de estudio y otras poblaciones a nivel mundial.xix, 121 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Maestría en InmunologíaDepartamento de MicrobiologíaFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::616 - EnfermedadesLeishmaniasisReceptor 3 Toll-LikeLeishmaniaLeishmaniasisToll-Like Receptor 3LeishmaniaLeishmaniaLRV1TLR3Leishmaniasis mucosaLeishmaniasis cutáneaPolimorfismo de nucleótido únicoColombiars3775296rs764010322rs3775291rs3775290Mucosal leishmaniasisCutaneous leishmaniasisSingle nucleotide polymorphismIdentificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1Identification and association of Toll-Like Receptor 3 polymorphisms with the development of mucosal Leishmaniasis against the coinfection Leishmania spp. - Leishmania RNA Virus 1Trabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMBiremeEl-Bendary, M., Neamatallah, M., Elalfy, H., Besheer, T., Elkholi, A., El-Diasty, M., Elsareef, M., Zahran, M., El-Aarag, B., Gomaa, A., Elhammady, D., El-Setouhy, M., Hegazy, A., & Esmat, G. (2018). The association of single nucleotide polymorphisms of Toll-like receptor 3, Toll-like receptor 7 and Toll-like receptor 8 genes with the susceptibility to HCV infection. British Journal of Biomedical Science, 75(4), 175–181. https://doi.org/10.1080/09674845.2018.1492186Engin, A., Arslan, S., Özbilüm, N., & Bakir, M. (2016). Is there any relationship between Toll-like receptor 3 c.1377C/T and −7C/A polymorphisms and susceptibility to Crimean Congo hemorrhagic fever? Journal of Medical Virology. https://doi.org/10.1002/jmv.24519Eren, R. O., Reverte, M., Rossi, M., Hartley, M. A., Castiglioni, P., Prevel, F., Martin, R., Desponds, C., Lye, L. F., Drexler, S. K., Reith, W., Beverley, S. M., Ronet, C., & Fasel, N. (2016). Mammalian Innate Immune Response to a Leishmania-Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence. Cell Host and Microbe, 20(3), 318–328. https://doi.org/10.1016/j.chom.2016.08.001Eshleman, E. M., Delgado, C., Kearney, S. J., Friedman, R. S., & Lenz, L. L. (2017). Down regulation of macrophage IFNGR1 exacerbates systemic L. monocytogenes infection. PLOS Pathogens, 13(5), e1006388. https://doi.org/10.1371/JOURNAL.PPAT.1006388Fahey, T. J., Tracey, K. J., Tekamp-Olson, P., Cousens, L. S., Jones, W. G., Shires, G. T., Cerami, A., & Sherry, B. (1992). Macrophage inflammatory protein 1 modulates macrophage function. Journal of Immunology (Baltimore, Md. : 1950), 148(9), 2764–2769. http://www.ncbi.nlm.nih.gov/pubmed/1573267Fairn, G. D., & Grinstein, S. (2012). How nascent phagosomes mature to become phagolysosomes. Trends in Immunology, 33(8), 397–405. https://doi.org/10.1016/j.it.2012.03.003Fan, L., Zhou, P., Hong, Q., Chen, A.-X., Liu, G.-Y., Yu, K.-D., & Shao, Z.-M. (2019). Toll-like receptor 3 acts as a suppressor gene in breast cancer initiation and progression: a two-stage association study and functional investigation. https://doi.org/10.1080/2162402X.2019.1593801Faraoni, I., Antonetti, F. R., Cardone, J., & Bonmassar, E. (2009). miR-155 gene: A typical multifunctional microRNA. In Biochimica et Biophysica Acta - Molecular Basis of Disease (Vol. 1792, Issue 6, pp. 497–505). Elsevier. https://doi.org/10.1016/j.bbadis.2009.02.013Ferro, C., López, M., Fuya, P., Lugo, L., Manuel Cordovez, J., & González, C. (2015). Spatial Distribution of Sand Fly Vectors and Eco-Epidemiology of Cutaneous Leishmaniasis Transmission in Colombia. https://doi.org/10.1371/journal.pone.0139391Filardy, A. A., Costa-Da-Silva, A. C., Koeller, C. M., Guimarães-Pinto, K., Ribeiro-Gomes, F. L., Lopes, M. F., Heise, N., Freire-De-Lima, C. G., Nunes, M. P., & DosReis, G. A. (2014). Infection with Leishmania major induces a cellular stress response in macrophages. PLoS ONE, 9(1). https://doi.org/10.1371/journal.pone.0085715Fischer, J., Koukoulioti, E., Schott, E., Fülöp, B., Heyne, R., Berg, T., & Bömmel, F. van. (2018). Polymorphisms in the Toll-like receptor 3 ( TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population. Scientific Reports 2018 8:1, 8(1), 1–8. https://doi.org/10.1038/s41598-018-31065-6Fox, J., & Bouchet-Valat, M. (2019). Rcmdr: R Commander. R package version 2.5-2. https://cran.r-project.org/web/packages/Rcmdr/Rcmdr.pdfGeng, P. L., Song, L. X., An, H., Huang, J. Y., Li, S., & Zeng, X. T. (2016). Toll-like receptor 3 is associated with the risk of HCV infection and HBV-related diseases. In Medicine (United States) (Vol. 95, Issue 21). Lippincott Williams and Wilkins. https://doi.org/10.1097/MD.0000000000002302Mukherjee, Suprabhat, Huda, S., & Sinha Babu, S. P. (2019). Toll-like receptor polymorphism in host immune response to infectious diseases: A review. Scandinavian Journal of Immunology, 90(1), 1–18. https://doi.org/10.1111/sji.12771Müller, K., Zandbergen, G., Hansen, B., Laufs, H., Jahnke, N., Solbach, W., & Laskay, T. (2001). Chemokines, natural killer cells and granulocytes in the early course of Leishmania major infection in mice. Medical Microbiology and Immunology, 190(1–2), 73–76. https://doi.org/10.1007/s004300100084Muñoz, G., & Davies, C. R. (2006). Leishmania panamensis transmission in the domestic environment: the results of a prospective epidemiological survey in Santander, Colombia. Biomédica, 26, 131–144. https://doi.org/10.7705/BIOMEDICA.V26I1.1507Murray, H. W. (2002). Kala-azar - Progress against a neglected disease. In New England Journal of Medicine (Vol. 347, Issue 22, pp. 1793–1794). https://doi.org/10.1056/NEJMe020133Murray, R. K., Kennelly, P. J., Bender, D. A., Rodwell, V. W., Botham, K. M., & Weil, P. A. (2013). Harper, Bioquímica ilustrada (2da edició). McGraw Hill.Nahum, A., Dadi, H., Bates, A., & Roifman, C. M. (2011). The L412F variant of Toll-like receptor 3 (TLR3) is associated with cutaneous candidiasis, increased susceptibility to cytomegalovirus, and autoimmunity. Journal of Allergy and Clinical Immunology, 127(2), 528–531. https://doi.org/10.1016/j.jaci.2010.09.03Nares, S., & Wahl, S. (2005). Monocytes and Macrophages. In Measuring Immunity: Basic Biology and Clinical Assessment (pp. 299–311). Academic Press. https://doi.org/10.1016/B978-012455900-4/50287-7NCBI. (2018). ClinVar; [VCV000792634.2]. https://www.ncbi.nlm.nih.gov/clinvar/variation/792634/NCBI. (2020). TLR3 toll like receptor 3 [ Homo sapiens (human) ] Gene ID: 7098. https://www.ncbi.nlm.nih.gov/gene/7098Ogg, M. M., Carrion, R., Botelho, A. C. de C., Mayrink, W., Correa-Oliveira, R., & Patterson, J. L. (2003). Short report: quantification of leishmaniavirus RNA in clinical samples and its possible role in pathogenesis. The American Journal of Tropical Medicine and Hygiene, 69(3), 309–313. http://www.ncbi.nlm.nih.gov/pubmed/14628949Okonechnikov, K., Golosova, O., & M, F. (2012). Unipro UGENE: a unified bioinformatics toolkit (38.1). Bioinformatics. https://doi.org/10.1093/bioinformatics/bts091Olivier, M. (2011). Host-pathogen interaction: Culprit within a culprit. Nature, 471(7337), 173–174. https://doi.org/10.1038/471173aOrganización Panamericana de la Salud. (2020). Leishmaniasis: Informe epidemiológico de las Américas. Núm. 9, diciembre del 2020. (Vol. 9). https://iris.paho.org/handle/10665.2/51742Ovalle-Bracho, C., Camargo, C., Díaz-Toro, Y., & Parra-Muñoz, M. (2018). Molecular typing of Leishmania (Leishmania) amazonensis and species of the subgenus Viannia associated with cutaneous and mucosal leishmaniasis in Colombia: A concordance study. Biomédica, 38(1), 86–95. https://doi.org/10.7705/BIOMEDICA.V38I0.3632Parra-Muñoz, M., Aponte, S., Ovalle-Bracho, C., Saavedra, C., & Echeverry, M. C. (2021). Detection of Leishmania RNA Virus in Clinical Samples from Cutaneous Leishmaniasis Patients Varies according to the Type of Sample. The American Journal of Tropical Medicine and Hygiene, 104(1), 233–239. https://doi.org/10.4269/ajtmh.20-0073Pauwels, A. M., Trost, M., Beyaert, R., & Hoffmann, E. (2017). Patterns, Receptors, and Signals: Regulation of Phagosome Maturation. In Trends in Immunology (Vol. 38, Issue 6, pp. 407–422). Elsevier Ltd. https://doi.org/10.1016/j.it.2017.03.006Pazmiño, Fredy A., Parra-Muñoz, M., Saavedra, C. H., Muvdi-Arenas, S., Ovalle-Bracho, C., & Echeverry, M. C. (2021). Leishmania RNA virus is associated with the occurrence of mucosal leishmaniasis caused by species from the Leishmania Viannia subgenus. [Artículo Sometido Para Publicación En American Journal of Tropical Medicine & Hygiene].Pazmiño, Fredy Alexander. (2020). Determinación de la asociación entre la presencia del Leishmaniavirus 1 (LRV-1) en parásitos infectantes de Leishmania spp y el desarrollo de la leishmaniasis mucosa en pacientes diagnosticados de leishmaniasis cutánea en Colombia. Universidad Nacional de Colombia.Perry, K., & Agabian, N. (1991). mRNA processing in the Trypanosomatidae. In Experientia (Vol. 47, Issue 2, pp. 118–128). Birkhäuser-Verlag. https://doi.org/10.1007/BF01945412Phan, L., Jin, Y., Zhang, H., Qiang, W., Shekhtman, E., Shao, D., Revoe, ., Villamarin, R., Ivanchenko, E., Kimura, M., Wang, Z. Y., Hao, L., Sharopova, N., Bihan, M., Sturcke, A., Lee, M., Popova, N., Wu, W., Bastiani, C., … Kattman, B. L. (2020). “ALFA: Allele Frequency Aggregator.” National Center for Biotechnology Information, U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/snp/docs/gsr/alfa/Poirier, V., & Av-Gay, Y. (2015). Intracellular Growth of Bacterial Pathogens: The Role of Secreted Effector Proteins in the Control of Phagocytosed Microorganisms. Microbiology Spectrum, 3(6). https://doi.org/10.1128/microbiolspec.vmbf-0003-2014Qi, R., Hoose, S., Schreiter, J., Sawant, K. V, Lamb, R., Ranjith-Kumar, C. T., Mills, J., San Mateo, L., Jordan, J. L., & Cheng Kao, C. (2010). Secretion of the Human Toll-like Receptor 3 Ectodomain Is Affected by Single Nucleotide Polymorphisms and Regulated by Unc93b1. The Journal of Biological Chemistry, 285(47), 36635–36644. https://doi.org/10.1074/jbc.M110.144402Raes, G., Beschin, A., Ghassabeh, G. H., & De Baetselier, P. (2007). Alternatively activated macrophages in protozoan infections. Current Opinion in Immunology, 19(4), 454–459. https://doi.org/10.1016/j.coi.2007.05.007Ranjith-Kumar, C. T., Miller, W., Sun, J., Xiong, J., Santos, J., Yarbrough, I., Lamb, R. J., Mills, J., Duffy, K. E., Hoose, S., Cunningham, M., Holzenburg, A., Mbow, M. L., Sarisky, R. T., & Kao, C. C. (2007). Effects of single nucleotide polymorphisms on toll-like receptor 3 activity and expression in cultured cells. Journal of Biological Chemistry, 282(24), 17696–17705. https://doi.org/10.1074/jbc.M700209200Rayamajhi, M., Humann, J., Penheiter, K., Andreasen, K., & Lenz, L. L. (2010). Induction of IFN-αβ enables Listeria monocytogenes to suppress macrophage activation by IFN-γ. The Journal of Experimental Medicine, 207(2), 327. https://doi.org/10.1084/JEM.20091746Rodríguez, G., Arenas, C., Ovalle, C., Hernández, C. A., & Camargo, C. (2016). La Leishmaniasis: Atllas y texto (C. A. Hernández (ed.)). Hospital Universitario Centro Dermatológico Federico Lleras Acosta, E.S.E.Rogers, L. (1904). PRELIMINARY NOTE ON THE DEVELOPMENT OF TRYPANOSOMA IN CULTURES OF THE CUNNINGHAM-LEISHMAN-DONOVAN BODIES OF CACHEXIAL FEVER AND KALA-AZAR. The Lancet, 164(4221), 215–216. https://doi.org/10.1016/S0140-6736(01)03458-4Rogers, L. (1906). Further work on the development of the hepatomonas of Kala-Azar and cachexial fever from Leishman-Donovan bodies. Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character, 77(517), 284–293. https://doi.org/10.1098/rspb.1906.0017Ross, M. R. (1903). Further notes on leishman’s bodies. British Medical Journal, 2(2239), 1401. https://doi.org/10.1136/bmj.2.2239.1401Rossi, M., Castiglioni, P., Hartley, M. A., Eren, R. O., Prével, F., Desponds, C., Utzschneider, D. T., Zehn, D., Cusi, M. G., Kuhlmann, F. M., Beverley, S. M., Ronet, C., & Fasel, N. (2017). Type I interferons induced by endogenous or exogenous viral infections promote metastasis and relapse of leishmaniasis. Proceedings of the National Academy of Sciences of the United States of America, 114(19), 4987–4992. https://doi.org/10.1073/pnas.1621447114Rossi, M., & Fasel, N. (2018). How to master the host immune system? Leishmania parasites have the solutions! International Immunology, 30(3), 103–111. https://doi.org/10.1093/INTIMM/DXX075Saiz, M., Llanos-Cuentas, A., Echevarria, J., Roncal, N., Cruz, M., Muniz, M. T., Lucas, C., Wirth, D. F., Scheffter, S., Magill, A. J., & Patterson, J. L. (1998). SHORT REPORT: DETECTION OF LEISHMANIAVIRUS IN HUMAN BIOPSY SAMPLES OF LEISHMANIASIS FROM PERU. In Am. J. Trop. Med. Hyg (Vol. 58, Issue 2).Santos, C. N. O., Ribeiro, D. R., Cardoso Alves, J., Cazzaniga, R. A., Magalhães, L. S., De Souza, M. S. F., Fonseca, A. B. L., Bispo, A. J. B., Porto, R. L. S., Santos, C. A. Dos, Da Silva, Â. M., Teixeira, M. M., De Almeida, R. P., & De Jesus, A. R. (2019). Association between Zika Virus Microcephaly in Newborns with the rs3775291 Variant in Toll-Like Receptor 3 and rs1799964 Variant at Tumor Necrosis Factor-α Gene. Journal of Infectious Diseases. https://doi.org/10.1093/infdis/jiz392Sassi, A., Louzir, H., Ben Salah, A., Mokni, M., Ben Osman, A., & Dellagi, K. (1999). Leishmanin skin test lymphoproliferative responses and cytokine production after symptomatic or asymptomatic Leishmania major infection in Tunisia. Clinical and Experimental Immunology, 116(1), 127–132. https://doi.org/10.1046/j.1365-2249.1999.00844.xScheffter, S. M., Ro, Y. T., Chung, I. K., & Patterson, J. L. (1995). The Complete Sequence of Leishmania RNA Virus LRV2-1, a Virus of an Old World Parasite Strain. Virology, 212(1), 84–90. https://doi.org/10.1006/viro.1995.1456Scheffter, S., Widmer, G., & Patterson, J. L. (1994). Complete Sequence of Leishmania RNA Virus 1-4 and Identification of Conserved Sequences. Virology, 199(2), 479–483. https://doi.org/10.1006/viro.1994.1149Schröder, N. W. J., & Schumann, R. R. (2005). Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. In Lancet Infectious Diseases (Vol. 5, Issue 3, pp. 156–164). Lancet Publishing Group. https://doi.org/10.1016/S1473-3099(05)01308-3Sghaier, I., Zidi, S., Mouelhi, L., Ghazoueni, E., Brochot, E., Almawi, W. Y., & Loueslati, B. Y. (2019). TLR3 and TLR4 SNP variants in the liver disease resulting from hepatitis B virus and hepatitis C virus infection. British Journal of Biomedical Science, 76(1), 35–41. https://doi.org/10.1080/09674845.2018.1547179Sironi, M., Biasin, M., Cagliani, R., Forni, D., De Luca, M., Saulle, I., Lo Caputo, S., Mazzotta, F., Macías, J., Pineda, J., Caruz, A., & Clerici, M. (2012). Natural Resistance to HIV-1 Infection Confers TLR3 A Common Polymorphism in. The Journal of Immunology, 188(2), 818–823. https://doi.org/10.4049/jimmunol.1102179Software MacKiev. (2021). GraphPad Prism (9.1.2). www.graphpad.comSong, G., Ouyang, G., & Bao, S. (2005). The activation of Akt/PKB signaling pathway and cell survival. In Journal of Cellular and Molecular Medicine (Vol. 9, Issue 1, pp. 59–71). Journal of Cellular and Molecular Medicine. https://doi.org/10.1111/j.1582-4934.2005.tb00337.xSong, G., Ouyang, G., & Bao, S. (2005). The activation of Akt/PKB signaling pathway and cell survival. In Journal of Cellular and Molecular Medicine (Vol. 9, Issue 1, pp. 59–71). Journal of Cellular and Molecular Medicine. https://doi.org/10.1111/j.1582-4934.2005.tb00337.xSong, G., Ouyang, G., & Bao, S. (2005). The activation of Akt/PKB signaling pathway and cell survival. In Journal of Cellular and Molecular Medicine (Vol. 9, Issue 1, pp. 59–71). Journal of Cellular and Molecular Medicine. https://doi.org/10.1111/j.1582-4934.2005.tb00337.xStuart, K. D., Weeks, R., Guilbride, L., & Myler, P. J. (1992). Molecular organization of Leishmania RNA virus 1. Proceedings of the National Academy of Sciences of the United States of America, 89(18), 8596–8600. https://doi.org/10.1073/pnas.89.18.8596Studzińska, M., Jabłońska, A., Wiśniewska-Ligier, M., Nowakowska, D., Gaj, Z., Leśnikowski, Z. J., Woźniakowska-Gęsicka, T., Wilczyński, J., & Paradowska, E. (2017). Association of TLR3 L412F Polymorphism with Cytomegalovirus Infection in Children. https://doi.org/10.1371/journal.pone.0169420Svensson, A., Tunbäck, P., Nordström, I., Padyukov, L., & Eriksson, K. (2012). Polymorphisms in Toll-like receptor 3 confer natural resistance to human herpes simplex virus type 2 infection. Journal of General Virology. https://doi.org/10.1099/vir.0.042572-0Tarr, P. I., Aline, R. F., Smiley, B. L., Scholler, J., Keithly, J., & Stuart, K. (1988). LR1: A candidate RNA virus of Leishmania. Proceedings of the National Academy of Sciences of the United States of America, 85(24), 9572–9275. https://doi.org/10.1073/pnas.85.24.9572Telleria, E. L., Martins-Da-Silva, A., Tempone, A. J., & Traub-Cseko, Y. M. (2018). Leishmania, microbiota and sand fly immunity. Parasitology, 145(10), 1336–1353. https://doi.org/10.1017/S0031182018001014Tripathi, P., Singh, V., & Naik, S. (2007). Immune response to leishmania: Paradox rather than paradigm. FEMS Immunology and Medical Microbiology, 51(2), 229–242. https://doi.org/10.1111/j.1574-695X.2007.00311.xUeno, N., & Wilson, M. E. (2012). Receptor-mediated phagocytosis of Leishmania: Implications for intracellular survival. Trends in Parasitology, 28(8), 335–344. https://doi.org/10.1016/j.pt.2012.05.002Ullah, M. O., Sweet, M. J., Mansell, A., Kellie, S., & Kobe, B. (2016). TRIF-dependent TLR signaling, its functions in host defense and inflammation, and its potential as a therapeutic target. Journal of Leukocyte Biology. https://doi.org/10.1189/jlb.2ri1115-531rUllah, M. O., Ve, T., Mangan, M., Alaidarous, M., Sweet, M. J., Mansell, A., & Kobe, B. (2013). The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain with structural similarity to IFIT proteins. Biological Crystallography , 69, 2420–2430. https://doi.org/10.1107/S0907444913022385UniProt. (n.d.). UniProtKB - O15455 (TLR3_HUMAN). Retrieved May 20, 2021, from https://www.uniprot.org/uniprot/O15455van Griensven, J., & Diro, E. (2012). Visceral Leishmaniasis. In Infectious Disease Clinics of North America (Vol. 26, Issue 2, pp. 309–322). Elsevier. https://doi.org/10.1016/j.idc.2012.03.005Vargas Córdoba, M. (2016). Virología médica (2da ed.). Universidad Nacional de Colombia y Manual Moderno.von Stebut, E., & Tenzer, S. (2018). Cutaneous leishmaniasis: Distinct functions of dendritic cells and macrophages in the interaction of the host immune system with Leishmania major. International Journal of Medical Microbiology, 308(1), 206–214. https://doi.org/10.1016/j.ijmm.2017.11.002Wang, B. G., Yi, D. H., & Liu, Y. F. (2015). TLR3 gene polymorphisms in cancer: A systematic review and meta-analysis. Chinese Journal of Cancer, 34(6). https://doi.org/10.1186/s40880-015-0020-zWang, Y., Liu, L., Davies, D. R., & Segal, D. M. (2010). Dimerization of Toll-like Receptor 3 (TLR3) Is Required for Ligand Binding. The Journal of Biological Chemistry, 285(47), 36836. https://doi.org/10.1074/JBC.M110.16797Weeks, R., Aline, R. F., Myler, P. J., & Stuart, K. (1992). LRV1 viral particles in Leishmania guyanensis contain double-stranded or single-stranded RNA. Journal of Virology, 66(3), 1389–1393. https://doi.org/10.1128/jvi.66.3.1389-1393.1992WHO. (2019). Leishmaniasis - Number of cases of cutaneus leishmaniasis: 2018. https://apps.who.int/neglected_diseases/ntddata/leishmaniasis/leishmaniasis.htmlWHO. (2021). Leishmaniasis. https://www.who.int/news-room/fact-sheets/detail/leishmaniasisWidmer, G., Comeau, A. M., Furlong, D. B., Wirth, D. F., & Patterson, J. L. (1989). Characterization of a RNA virus from the parasite Leishmania. Proceedings of the National Academy of Sciences of the United States of America, 86(15), 5979–5982. https://doi.org/10.1073/pnas.86.15.5979Widmer, G., & Dooley, S. (1995). Phylogenetic analysis of Leishmania RNA virus and Leishmania suggests ancient virus-p3arasite association. In rNucleic Acids Research (Vol. 23, Issue 12).Xia, D., Ye, S., Zhang, X., bao Zhang, Y., Tian, X., Liu, A., Cui, C., & Shi, L. (2020). Association of TLR3 (rs3775291) and IL-10 (rs1800871) gene polymorphisms with susceptibility to Hepatitis B infection: A meta-analysis. Epidemiology and Infection, 148, 1–11. https://doi.org/10.1017/S0950268820002101Yang, C. A., Raftery, M. J., Hamann, L., Guerreiro, M., Grütz, G., Haase, D., Unterwalder, N., Schönrich, G., Schumann, R. R., Volk, H. D., & Scheibenbogen, C. (2012). Association of TLR3-hyporesponsiveness and functional TLR3 L412F polymorphism with recurrent herpes labialis. Human Immunology, 73(8), 844–851. https://doi.org/10.1016/j.humimm.2012.04.008Ye, N., Ding, Y., Wild, C., Shen, Q., & Zhou, J. (2014). Small molecule inhibitors targeting activator protein 1 (AP-1). Journal of Medicinal Chemistry, 57(16), 6930–6948. https://doi.org/10.1021/JM5004733Zayed, R. A., Omran, D., Mokhtar, D. A., Zakaria, Z., Ezzat, S., Soliman, M. A., Mobarak, L., El-Sweesy, H., & Emam, G. (2017). Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients. Am. J. Trop. Med. Hyg, 96(3), 720–726. https://doi.org/10.4269/ajtmh.16-0644Zhou, P., Fan, L., Yu, K.-D., Zhao, M.-W., & Li, X.-X. (2011). Toll-like receptor 3 C1234T may protect against geographic atrophy through decreased dsRNA binding capacity. The FASEB Journal, 25(10), 3489–3495. https://doi.org/10.1096/FJ.11-189258Zilberstein, & Dwyer. (1988). Identification of a surface membrane proton-translocating ATPase in promastigotes of the parasitic protozoan Leishmania donovani. Biochemical Journal, 256(1), 13–21. https://doi.org/10.1042/bj2560013Zilberstein, Philosoph, & Gepstein. (1989). Maintenance of cytoplasmic pH and proton motive force in promastigotes of Leishmania donovani. Molecular and Biochemical Parasitology, 36(2), 109–117. https://doi.org/10.1016/0166-6851(89)90183-7Abbas, A., Litchtman, A., & Pillai, S. (2015). Inmunología celular y molecular. In El Sevier (8va ed.).Agudelo Chivatá, N. J. (2019a). Informe de evento: Leishmaniasis cutánea.Agudelo Chivatá, N. J. (2019b). Informe de evento: Leishmaniasis mucosa.Agudelo, S., & Robledo, S. (2000). Revisión de tema: respuesta inmune en infecciones humanas por Leishmania spp. Iatreia, 13(3), 167–178Akashi-Takamura, S., & Miyake, K. (2006). Toll-like receptors (TLRs) and immune disorders. In Journal of Infection and Chemotherapy (Vol. 12, Issue 5, pp. 233–240). Springer Japan. https://doi.org/10.1007/s10156-006-0477-4Alagarasu, K., Bachal, R. V., Memane, R. S., Shah, P. S., & Cecilia, D. (2015). Polymorphisms in RNA sensing toll like receptor genes and its association with clinical outcomes of dengue virus infection. Immunobiology, 220(1), 164–168. https://doi.org/10.1016/J.IMBIO.2014.09.020Alcolea, P. J., Alonso, A., Gómez, M. J., Postigo, M., Molina, R., Jiménez, M., & Larraga, V. (2014). Stage-specific differential gene expression in Leishmania infantum: From the foregut of Phlebotomus perniciosus to the human phagocyte. BMC Genomics, 15(1). https://doi.org/10.1186/1471-2164-15-849Alexander, J., & Russell, D. G. (1992). The Interaction of Leishmania Species with Macrophages. Advances in Parasitology, 31(C), 175–254. https://doi.org/10.1016/S0065-308X(08)60022-6Alipoor, B., Ghaedi, H., Davood Omrani, M., Bastami, M., Meshkani, R., & Golmohammadi, T. (2016). A Bioinformatics Approach to Prioritize Single Nucleotide Polymorphisms in TLRs Signaling Pathway Genes. Internationa Journal of Molecular and Celular Medicine, 5(2). http://compbio.uthsc.edu/miRSNP/Arbour, N. C., Lorenz, E., Schutte, B. C., Zabner, J., Kline, J. N., Jones, M., Frees, K., Watt, J. L., & Schwartz, D. A. (2000). TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nature Genetics, 25(2), 187–191. https://doi.org/10.1038/76048Aronson, N., Herwaldt, B. L., Libman, M., Pearson, R., Lopez-Velez, R., Weina, P., Carvalho, E., Ephros, M., Jeronimo, S., & Magill, A. (2017). Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). The American Journal of Tropical Medicine and Hygiene, 96(1), 24. https://doi.org/10.4269/AJTMH.16-84256Atayde, V. D., da Silva Lira Filho, A., Chaparro, V., Zimmermann, A., Martel, C., Jaramillo, M., & Olivier, M. (2019). Exploitation of the Leishmania exosomal pathway by Leishmania RNA virus 1. Nature Microbiology, 4(4), 714–723. https://doi.org/10.1038/s41564-018-0352-yAtsaves, V., Leventaki, V., Rassidakis, G. Z., & Claret, F. X. (2019). AP-1 Transcription Factors as Regulators of Immune Responses in Cancer. Cancers, 11(7). https://doi.org/10.3390/CANCERS11071037Avendaño-Tamayo, E., Rúa, A., Parra-Marín, M. V., Rojas, W., Campo, O., Chacón-Duque, J., Agudelo-Flórez, P., Narváez, C. F., Salgado, D. M., Restrepo, B. N., & Bedoya, G. (2019). Evaluation of variants in IL6R, TLR3, and DC-SIGN genes associated with dengue in a sampled Colombian population. Biomedica, 39(1), 88–101. https://doi.org/10.7705/biomedica.v39i1.4029Awasthi, A., Mathur, R. K., & Saha, B. (2004). Immune response to Leishmania infection. Indian Journal of Medical Research, 119(6), 238–258.Azambuja, P., Garcia, E. S., & Ratcliffe, N. A. (2005). Gut microbiota and parasite transmission by insect vectors. Trends in Parasitology, 21(12), 568–572. https://doi.org/10.1016/j.pt.2005.09.011Bailey, M. S., & Lockwood, D. N. J. (2007). Cutaneous leishmaniasis. Clinics in Dermatology, 25(2), 203–211. https://doi.org/10.1016/j.clindermatol.2006.05.008Bañuls, A. L., Hide, M., & Prugnolle, F. (2007). Leishmania and the Leishmaniases: A Parasite Genetic Update and Advances in Taxonomy, Epidemiology and Pathogenicity in Humans. Advances in Parasitology, 64, 1–109. https://doi.org/10.1016/S0065-308X(06)64001-3Bell, J. K., Botos, I., Hall, P. R., Askins, J., Shiloach, J., Davies, D. R., & Segal, D. M. (2006). The molecular structure of the TLR3 extracellular domain. Journal of Endotoxin Research, 12(6), 375–378. https://doi.org/10.1177/09680519060120060801Bogdan, C., & Röllinghoff, M. (1998). The immune response to Leishmania: Mechanisms of parasite control and evasion. International Journal for Parasitology, 28(1), 121–134. https://doi.org/10.1016/S0020-7519(97)00169-0Bruschi, F., & Gradoni, L. (2018). The leishmaniases: Old neglected tropical diseases. In The Leishmaniases: Old Neglected Tropical Diseases. Springer International Publishing. https://doi.org/10.1007/978-3-319-72386-0Cadd, T. L., Keenan, M. C., & Pattersonl, J. L. (1993). Detection of Leishmania RNA Virus 1 Proteins. In JOURNAL OF VIROLOGY. http://jvi.asm.org/Cantanhêde, L. M., da Silva Júnior, C. F., Ito, M. M., Felipin, K. P., Nicolete, R., Salcedo, J. M. V., Porrozzi, R., Cupolillo, E., & Ferreira, R. de G. M. (2015). Further Evidence of an Association between the Presence of Leishmania RNA Virus 1 and the Mucosal Manifestations in Tegumentary Leishmaniasis Patients. PLOS Neglected Tropical Diseases, 9(9), e0004079. https://doi.org/10.1371/journal.pntd.0004079CDC. (n.d.). CDC - Leishmaniasis - Biology. Retrieved February 27, 2020, from https://www.cdc.gov/parasites/leishmaniasis/biology.htmlCenters for disease control and prevention (CDC). (2020, February 14). CDC - Leishmaniasis. https://www.cdc.gov/parasites/leishmaniasis/index.htmlChattopadhyay, S., & Sen, G. C. (2014). dsRNA-Activation of TLR3 and RLR Signaling: Gene Induction-Dependent and Independent Effects. Journal of Interferon & Cytokine Research, 34(6), 436. https://doi.org/10.1089/JIR.2014.0034Chaudhuri, G., Chaudhuri, M., Pan, A., & Chang, K.-P. (1989). Surface Acid Proteinase (gp63) of Leishmania mexicana. The Journal of Biological Chemestry, 264(13), 7483–7489.Chen, B., Cole, J. W., & Grond-Ginsbach, C. (2017). Departure from Hardy Weinberg Equilibrium and Genotyping Error. Frontiers in Genetics, 8(OCT), 167. https://doi.org/10.3389/FGENE.2017.00167Chieco, P., & Derenzini, M. (1999). The Feulgen reaction 75 years on. Histochemistry and Cell Biology, 111(5), 345–358. https://doi.org/10.1007/s004180050367Choe, J., Kelker, M. S., & Wilson, I. A. (2005). Crystal Structure of Human Toll-Like Receptor 3 (TLR3) Ectodomain. Science, 309(5734), 581–585. https://doi.org/10.1126/science.1115253Coombs, G., & North, M. (2004). Biochemical Protozoology. In Journal of Chemical Information and Modeling. Taylor & Francis. https://doi.org/10.1017/CBO9781107415324.004Corthay, A. (2006). A three-cell model for activation of naïve T helper cells. Scandinavian Journal of Immunology, 64(2), 93–96. https://doi.org/10.1111/j.1365-3083.2006.01782.xCroft, S. L., & Molyneux, D. H. (1979). Studies on the ultrastructure, virus-like particles and infectivity of Leishmania hertigi. Annals of Tropical Medicine and Parasitology, 73(3), 213–226. https://doi.org/10.1080/00034983.1979.11687251Cruz-Barrera, M. L., Ovalle-Bracho, C., Ortegon-Vergara, V., Pérez-Franco, J. E., & Echeverry, M. C. (2015). Improving Leishmania species identification in different types of samples from cutaneous lesions. Journal of Clinical Microbiology, 53(4), 1339–1341. https://doi.org/10.1128/JCM.02955-14David, C. V., & Craft, N. (2009). Cutaneous and mucocutaneous leishmaniasis. Dermatologic Therapy, 22(6), 491–502. https://doi.org/10.1111/j.1529-8019.2009.01272.xde Carvalho, R. V. H., Andrade, W. A., Lima-Junior, D. S., Dilucca, M., de Oliveira, C. V., Wang, K., Nogueira, P. M., Rugani, J. N., Soares, R. P., Beverley, S. M., Shao, F., & Zamboni, D. S. (2019). Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome. Cell Reports, 26(2), 429-437.e5. https://doi.org/10.1016/J.CELREP.2018.12.047de Carvalho, R. V. H., Lima-Junior, D. S., da Silva, M. V. G., Dilucca, M., Rodrigues, T. S., Horta, C. V., Silva, A. L. N., da Silva, P. F., Frantz, F. G., Lorenzon, L. B., Souza, M. M., Almeida, F., Cantanhêde, L. M., Ferreira, R. de G. M., Cruz, A. K., & Zamboni, D. S. (2019). Leishmania RNA virus exacerbates Leishmaniasis by subverting innate immunity via TLR3-mediated NLRP3 inflammasome inhibition. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-13356-2de Carvalho, R. V. H., Lima-Júnior, D. S., de Oliveira, C. V., & Zamboni, D. S. (2021). Endosymbiotic RNA virus inhibits Leishmania-induced caspase-11 activation. IScience, 24(1), 102004. https://doi.org/10.1016/J.ISCI.2020.102004de Souza, M. M., Manzine, L. R., da Silva, M. V. G., Bettini, J., Portugal, R. V., Cruz, A. K., Arruda, E., & Thiemann, O. H. (2014). An improved purification procedure for Leishmania RNA virus (LRV). Brazilian Journal of Microbiology, 45(2), 695–698. https://doi.org/10.1590/S1517-83822014000200044Deeba, E., Koptides, D., Lambrianides, A., Pantzaris, M., Krashias, G., & Christodoulou, C. (2019). Complete sequence analysis of human toll-like receptor 3 gene in natural killer cells of multiple sclerosis patients. Multiple Sclerosis and Related Disorders, 33(May), 100–106. https://doi.org/10.1016/j.msard.2019.05.027Dermine, J.-F., Duclos, S., rome Garin, J., ois St-Louis, F., Rea, S., Parton, R. G., & Desjardins, M. (2001). Flotillin-1-enriched Lipid Raft Domains Accumulate on Maturing Phagosomes* Downloaded from. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 276(21), 18507–18512. https://doi.org/10.1074/jbc.M101113200Dowlati, Y. (1996). Cutaneous leishmaniasis: Clinical aspect. Clinics in Dermatology, 14(5), 425–431. https://doi.org/10.1016/0738-081X(96)00058-2Dutta, S. K., & Tripathi, A. (2017). Association of toll-like receptor polymorphisms with susceptibility to chikungunya virus infection. Virology. https://doi.org/10.1016/j.virol.2017.08.009Ehrchen, J. M., Roebrock, K., Foell, D., Nippe, N., von Stebut, E., Weiss, J. M., Münck, N. A., Viemann, D., Varga, G., Müller-Tidow, C., Schuberth, H. J., Roth, J., & Sunderkötter, C. (2010). Keratinocytes determine Th1 immunity during early experimental leishmaniasis. PLoS Pathogens, 6(4), 1–16. https://doi.org/10.1371/journal.ppat.1000871Ministerio de Ciencia Tecnología e InnovaciónUniversidad Nacional de ColombiaEstudiantesInvestigadoresMaestrosLICENSElicense.txtlicense.txttext/plain; charset=utf-84074https://repositorio.unal.edu.co/bitstream/unal/80802/1/license.txt8153f7789df02f0a4c9e079953658ab2MD51ORIGINAL1032473343.2021.pdf1032473343.2021.pdfTesis de Maestría en Inmunologíaapplication/pdf3228997https://repositorio.unal.edu.co/bitstream/unal/80802/2/1032473343.2021.pdf2d1158c59206e6ba4fc26d1246fb1f2bMD52THUMBNAIL1032473343.2021.pdf.jpg1032473343.2021.pdf.jpgGenerated Thumbnailimage/jpeg5087https://repositorio.unal.edu.co/bitstream/unal/80802/3/1032473343.2021.pdf.jpgb78b034bf354cec7c09f926dc98cadc4MD53unal/80802oai:repositorio.unal.edu.co:unal/808022024-08-01 23:10:44.314Repositorio Institucional Universidad Nacional de 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EVESURBIFBPUiBMQSBTRUNSRVRBUsONQSBHRU5FUkFMLiAqTEEgVEVTSVMgQSBQVUJMSUNBUiBERUJFIFNFUiBMQSBWRVJTScOTTiBGSU5BTCBBUFJPQkFEQS4gCgpBbCBoYWNlciBjbGljIGVuIGVsIHNpZ3VpZW50ZSBib3TDs24sIHVzdGVkIGluZGljYSBxdWUgZXN0w6EgZGUgYWN1ZXJkbyBjb24gZXN0b3MgdMOpcm1pbm9zLiBTaSB0aWVuZSBhbGd1bmEgZHVkYSBzb2JyZSBsYSBsaWNlbmNpYSwgcG9yIGZhdm9yLCBjb250YWN0ZSBjb24gZWwgYWRtaW5pc3RyYWRvciBkZWwgc2lzdGVtYS4KClVOSVZFUlNJREFEIE5BQ0lPTkFMIERFIENPTE9NQklBIC0gw5psdGltYSBtb2RpZmljYWNpw7NuIDE5LzEwLzIwMjEK

Identificación y asociación de polimorfismos de Toll-Like Receptor 3 con el desarrollo de Leishmaniasis mucosa frente a la coinfección Leishmania spp. – Leishmania RNA Virus 1

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