Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2

A dysregulated or exacerbated inflammatory response is thought to be the key driver of the pathogenesis of severe disease caused by the mosquito-borne dengue virus (DENV). Compounds that restrict virus replication and modulate the inflammatory response could thus serve as promising therapeutics miti...

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Autores:: Castillo, Jorge Andrés
Giraldo, Diana M
Hernández López, Juan Carlos
M. Smit, Jolanda
Rodenhuis-Zybert, Izabela A.
Urcuqui-Inchima, Silvio

Tipo de recurso:: Article of investigation

Fecha de publicación:: 2021

Institución:: Universidad Cooperativa de Colombia

Repositorio:: Repositorio UCC

Idioma:

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network_acronym_str	COOPER2
network_name_str	Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2
title	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2
spellingShingle	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2 innate immune responses macrophages vitamin D dengue virus 2
title_short	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2
title_full	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2
title_fullStr	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2
title_full_unstemmed	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2
title_sort	Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2
dc.creator.fl_str_mv	Castillo, Jorge Andrés Giraldo, Diana M Hernández López, Juan Carlos M. Smit, Jolanda Rodenhuis-Zybert, Izabela A. Urcuqui-Inchima, Silvio
dc.contributor.author.none.fl_str_mv	Castillo, Jorge Andrés Giraldo, Diana M Hernández López, Juan Carlos M. Smit, Jolanda Rodenhuis-Zybert, Izabela A. Urcuqui-Inchima, Silvio
dc.subject.spa.fl_str_mv	innate immune responses macrophages vitamin D dengue virus 2
topic	innate immune responses macrophages vitamin D dengue virus 2
description	A dysregulated or exacerbated inflammatory response is thought to be the key driver of the pathogenesis of severe disease caused by the mosquito-borne dengue virus (DENV). Compounds that restrict virus replication and modulate the inflammatory response could thus serve as promising therapeutics mitigating the disease pathogenesis. We and others have previously shown that macrophages, which are important cellular targets for DENV replication, differentiated in the presence of bioactive vitamin D (VitD3) are less permissive to viral replication, and produce lower levels of pro-inflammatory cytokines. Therefore, we here evaluated the extent and kinetics of innate immune responses of DENV-2 infected monocytes differentiated into macrophages in the presence (D3-MDMs) or absence of VitD3 (MDMs). We found that D3-MDMs expressed lower levels of RIG I, Toll-like receptor (TLR) 3, and TLR7, as well as higher levels of SOCS-1 in response to DENV-2 infection. D3- MDMs produced lower levels of reactive oxygen species, related to a lower expression of TLR9. Moreover, although VitD3 treatment did not modulate either the expression of IFN-α or IFN-β, higher expression of protein kinase R (PKR) and 20 -50 -oligoadenylate synthetase 1 (OAS1) mRNA were found in D3-MDMs. Importantly, the observed effects were independent of reduced infection, highlighting the intrinsic differences between D3-MDMs and MDMs. Taken together, our results suggest that differentiation of MDMs in the presence of VitD3 modulates innate immunity in responses to DENV-2 infection
publishDate	2021
dc.date.issued.none.fl_str_mv	2021-10-11
dc.date.accessioned.none.fl_str_mv	2022-07-31T17:31:25Z
dc.date.available.none.fl_str_mv	2022-07-31T17:31:25Z
dc.type.none.fl_str_mv	Artículos Científicos
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dc.identifier.uri.spa.fl_str_mv	10.1371/journal.pntd.0009873
dc.identifier.uri.none.fl_str_mv	https://hdl.handle.net/20.500.12494/45972
dc.identifier.bibliographicCitation.spa.fl_str_mv	Castillo JA, Giraldo DM, Hernandez JC, Smit JM, Rodenhuis-Zybert IA, Urcuqui-Inchima S (2021) Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2. PLoS Negl Trop Dis 15(10): e0009873. https://doi.org/ 10.1371/journal.pntd.0009873
identifier_str_mv	10.1371/journal.pntd.0009873 Castillo JA, Giraldo DM, Hernandez JC, Smit JM, Rodenhuis-Zybert IA, Urcuqui-Inchima S (2021) Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2. PLoS Negl Trop Dis 15(10): e0009873. https://doi.org/ 10.1371/journal.pntd.0009873
url	https://hdl.handle.net/20.500.12494/45972
dc.relation.ispartofjournal.spa.fl_str_mv	PLOS NEGLECTED TROPICAL DISEASES
dc.relation.references.spa.fl_str_mv	Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013; 496: 504–7. https://doi.org/10.1038/nature12060 PMID: 23563266 . (WHO) WHO. Dengue. Guidelines for diagnosis, treatment, prevention and control. 2009. (WHO) WHO. Dengue vaccine: WHO position paper–July 2016. Wkly Epidemiol Rec. 2016; 91: 349– 64. https://doi.org/10.1371/jour PMID: 27476189 Guzman MG, Harris E. Dengue. Lancet. 2014; 6736: 1–13. https://doi.org/10.1016/S0140-6736(14) 60572-9 Nasirudeen a M a, Wong HH, Thien P, Xu S, Lam K-P, Liu DX. RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. PLoS Negl Trop Dis. 2011; 5: 1–11. https:// doi.org/10.1371/journal.pntd.0000926 PMID: 21245912 Tsai Y-T, Chang S-Y, Lee C-N, Kao C-L. Human TLR3 recognizes dengue virus and modulates viral replication in vitro. Cell Microbiol. 2009; 11: 604–15. https://doi.org/10.1111/j.1462-5822.2008.01277.x PMID: 19134117 Wang JP, Liu P, Latz E, Golenbock DT, Finberg RW, Libraty DH. Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition. J Immunol. 2006; 177: 7114–21. Available: http://www.ncbi.nlm.nih.gov/pubmed/17082628 https://doi.org/10.4049/ jimmunol.177.10.7114 PMID: 17082628 Pagni S, Fernandez-Sesma A. Evasion of the human innate immune system by dengue virus. Immunol Res. 2012; 54: 152–9. https://doi.org/10.1007/s12026-012-8334-2 PMID: 22569913 Butthep P, Chunhakan S, Yoksan S, Tangnararatchakit K, Chuansumrit A. Alteration of cytokines and chemokines during febrile episodes associated with endothelial cell damage and plasma leakage in dengue hemorrhagic fever. Pediatr Infect Dis J. 2012; 31: 232–238. https://doi.org/10.1097/INF. 0b013e31826fd456 PMID: 22926216 Malavige GN, Ogg GS. Pathogenesis of vascular leak in dengue virus infection. Immunology. 2017; 151: 261–269. https://doi.org/10.1111/imm.12748 PMID: 28437586 White JH. Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect Immun. 2008; 76: 3837–43. https://doi.org/10.1128/IAI.00353-08 PMID: 18505808 Gal-Tanamy M, Bachmetov L, Ravid A, Koren R, Erman A, Tur-Kaspa R, et al. Vitamin D: an innate antiviral agent suppressing hepatitis C virus in human hepatocytes. Hepatology. 2011; 54: 1570–9. https://doi.org/10.1002/hep.24575 PMID: 21793032 Lai H, Detrick B, Fishman EK, Gerstenblith G, Brinker JA, Hollis BW, et al. Vitamin D deficiency is associated with the development of subclinical coronary artery disease in African Americans with HIV infection: a preliminary study. J Investig Med. 2012; 60: 801–7. https://doi.org/10.2310/JIM. 0b013e318250bf99 PMID: 22481166 Hansdottir S, Monick MM, Lovan N, Powers L, Gerke A, Hunninghake GW. Vitamin D decreases respiratory syncytial virus induction of NF-kappaB-linked chemokines and cytokines in airway epithelium while maintaining the antiviral state. J Immunol. 2010; 184: 965–74. https://doi.org/10.4049/jimmunol. 0902840 PMID: 20008294 Jadhav NJ, Gokhale S, Seervi M, Patil PS, Alagarasu K. Immunomodulatory effect of 1, 25 dihydroxy vitamin D3on the expression of RNA sensing pattern recognition receptor genes and cytokine response in dengue virus infected U937-DC-SIGN cells and THP-1 macrophages. Int Immunopharmacol. 2018; 62: 237–243. https://doi.org/10.1016/j.intimp.2018.07.019 PMID: 30032048 Puerta-Guardo H, Medina F, De la Cruz Herna´ndez SI, Rosales VH, Ludert JE, del Angel RM. The 1α,25-dihydroxy-vitamin D3 reduces dengue virus infection in human myelomonocyte (U937) and hepatic (Huh-7) cell lines and cytokine production in the infected monocytes. Antiviral Res. 2012; 94: 57–61. https://doi.org/10.1016/j.antiviral.2012.02.006 PMID: 22387385 Arboleda Alzate JF, Rodenhuis-Zybert IA, Herna´ndez JC, Smit JM, Urcuqui-Inchima S. Human macrophages differentiated in the presence of vitamin D3restrict dengue virus infection and innate responses by downregulating mannose receptor expression. PLoS Negl Trop Dis. 2017; 11: 1–18. https://doi.org/ 10.1371/journal.pntd.0005904 PMID: 29020083 Giraldo DM, Cardona A, Urcuqui-Inchima S. High-dose of vitamin D supplement is associated with reduced susceptibility of monocyte-derived macrophages to dengue virus infection and pro-inflammatory cytokine production: An exploratory study. Clin Chim Acta. 2018; 478: 140–151. https://doi.org/10. 1016/j.cca.2017.12.044 PMID: 29289621
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dc.publisher.spa.fl_str_mv	Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000
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spelling	Castillo, Jorge AndrésGiraldo, Diana MHernández López, Juan Carlos M. Smit, JolandaRodenhuis-Zybert, Izabela A.Urcuqui-Inchima, Silvio15 (10)2022-07-31T17:31:25Z2022-07-31T17:31:25Z2021-10-1110.1371/journal.pntd.0009873https://hdl.handle.net/20.500.12494/45972Castillo JA, Giraldo DM, Hernandez JC, Smit JM, Rodenhuis-Zybert IA, Urcuqui-Inchima S (2021) Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2. PLoS Negl Trop Dis 15(10): e0009873. https://doi.org/ 10.1371/journal.pntd.0009873A dysregulated or exacerbated inflammatory response is thought to be the key driver of the pathogenesis of severe disease caused by the mosquito-borne dengue virus (DENV). Compounds that restrict virus replication and modulate the inflammatory response could thus serve as promising therapeutics mitigating the disease pathogenesis. We and others have previously shown that macrophages, which are important cellular targets for DENV replication, differentiated in the presence of bioactive vitamin D (VitD3) are less permissive to viral replication, and produce lower levels of pro-inflammatory cytokines. Therefore, we here evaluated the extent and kinetics of innate immune responses of DENV-2 infected monocytes differentiated into macrophages in the presence (D3-MDMs) or absence of VitD3 (MDMs). We found that D3-MDMs expressed lower levels of RIG I, Toll-like receptor (TLR) 3, and TLR7, as well as higher levels of SOCS-1 in response to DENV-2 infection. D3- MDMs produced lower levels of reactive oxygen species, related to a lower expression of TLR9. Moreover, although VitD3 treatment did not modulate either the expression of IFN-α or IFN-β, higher expression of protein kinase R (PKR) and 20 -50 -oligoadenylate synthetase 1 (OAS1) mRNA were found in D3-MDMs. Importantly, the observed effects were independent of reduced infection, highlighting the intrinsic differences between D3-MDMs and MDMs. Taken together, our results suggest that differentiation of MDMs in the presence of VitD3 modulates innate immunity in responses to DENV-2 infectionhttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000283088http://orcid.org/0000-0002-9200-5698https://scienti.colciencias.gov.co/gruplac/jsp/visualiza/visualizagr.jsp?nro=00000000011355juankhernandez@gmail.com1-21Universidad Cooperativa de Colombia, Facultad de Ciencias de la Salud, Programa de Medicina, Medellín y Envigado, Colombia, 00000MedicinaMedellíninnate immune responsesmacrophagesvitamin Ddengue virus 2Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2Artículos Científicoshttp://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionAtribucióninfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PLOS NEGLECTED TROPICAL DISEASESBhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013; 496: 504–7. https://doi.org/10.1038/nature12060 PMID: 23563266. (WHO) WHO. Dengue. Guidelines for diagnosis, treatment, prevention and control. 2009.(WHO) WHO. Dengue vaccine: WHO position paper–July 2016. Wkly Epidemiol Rec. 2016; 91: 349– 64. https://doi.org/10.1371/jour PMID: 27476189Guzman MG, Harris E. Dengue. Lancet. 2014; 6736: 1–13. https://doi.org/10.1016/S0140-6736(14) 60572-9Nasirudeen a M a, Wong HH, Thien P, Xu S, Lam K-P, Liu DX. RIG-I, MDA5 and TLR3 synergistically play an important role in restriction of dengue virus infection. PLoS Negl Trop Dis. 2011; 5: 1–11. https:// doi.org/10.1371/journal.pntd.0000926 PMID: 21245912Tsai Y-T, Chang S-Y, Lee C-N, Kao C-L. Human TLR3 recognizes dengue virus and modulates viral replication in vitro. Cell Microbiol. 2009; 11: 604–15. https://doi.org/10.1111/j.1462-5822.2008.01277.x PMID: 19134117Wang JP, Liu P, Latz E, Golenbock DT, Finberg RW, Libraty DH. Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition. J Immunol. 2006; 177: 7114–21. Available: http://www.ncbi.nlm.nih.gov/pubmed/17082628 https://doi.org/10.4049/ jimmunol.177.10.7114 PMID: 17082628Pagni S, Fernandez-Sesma A. Evasion of the human innate immune system by dengue virus. Immunol Res. 2012; 54: 152–9. https://doi.org/10.1007/s12026-012-8334-2 PMID: 22569913Butthep P, Chunhakan S, Yoksan S, Tangnararatchakit K, Chuansumrit A. Alteration of cytokines and chemokines during febrile episodes associated with endothelial cell damage and plasma leakage in dengue hemorrhagic fever. Pediatr Infect Dis J. 2012; 31: 232–238. https://doi.org/10.1097/INF. 0b013e31826fd456 PMID: 22926216Malavige GN, Ogg GS. Pathogenesis of vascular leak in dengue virus infection. Immunology. 2017; 151: 261–269. https://doi.org/10.1111/imm.12748 PMID: 28437586White JH. Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect Immun. 2008; 76: 3837–43. https://doi.org/10.1128/IAI.00353-08 PMID: 18505808Gal-Tanamy M, Bachmetov L, Ravid A, Koren R, Erman A, Tur-Kaspa R, et al. Vitamin D: an innate antiviral agent suppressing hepatitis C virus in human hepatocytes. Hepatology. 2011; 54: 1570–9. https://doi.org/10.1002/hep.24575 PMID: 21793032Lai H, Detrick B, Fishman EK, Gerstenblith G, Brinker JA, Hollis BW, et al. Vitamin D deficiency is associated with the development of subclinical coronary artery disease in African Americans with HIV infection: a preliminary study. J Investig Med. 2012; 60: 801–7. https://doi.org/10.2310/JIM. 0b013e318250bf99 PMID: 22481166Hansdottir S, Monick MM, Lovan N, Powers L, Gerke A, Hunninghake GW. Vitamin D decreases respiratory syncytial virus induction of NF-kappaB-linked chemokines and cytokines in airway epithelium while maintaining the antiviral state. J Immunol. 2010; 184: 965–74. https://doi.org/10.4049/jimmunol. 0902840 PMID: 20008294Jadhav NJ, Gokhale S, Seervi M, Patil PS, Alagarasu K. Immunomodulatory effect of 1, 25 dihydroxy vitamin D3on the expression of RNA sensing pattern recognition receptor genes and cytokine response in dengue virus infected U937-DC-SIGN cells and THP-1 macrophages. Int Immunopharmacol. 2018; 62: 237–243. https://doi.org/10.1016/j.intimp.2018.07.019 PMID: 30032048Puerta-Guardo H, Medina F, De la Cruz Herna´ndez SI, Rosales VH, Ludert JE, del Angel RM. The 1α,25-dihydroxy-vitamin D3 reduces dengue virus infection in human myelomonocyte (U937) and hepatic (Huh-7) cell lines and cytokine production in the infected monocytes. Antiviral Res. 2012; 94: 57–61. https://doi.org/10.1016/j.antiviral.2012.02.006 PMID: 22387385Arboleda Alzate JF, Rodenhuis-Zybert IA, Herna´ndez JC, Smit JM, Urcuqui-Inchima S. Human macrophages differentiated in the presence of vitamin D3restrict dengue virus infection and innate responses by downregulating mannose receptor expression. PLoS Negl Trop Dis. 2017; 11: 1–18. https://doi.org/ 10.1371/journal.pntd.0005904 PMID: 29020083Giraldo DM, Cardona A, Urcuqui-Inchima S. High-dose of vitamin D supplement is associated with reduced susceptibility of monocyte-derived macrophages to dengue virus infection and pro-inflammatory cytokine production: An exploratory study. 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Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2

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