Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1

ABSTRACT: Hematopoietic stem cells (HSCs), a multipotent and self-renewing population responsible for the generation and maintenance of blood cells, have been the subject of numerous investigations due to their therapeutic potential. It has been shown that these cells are able to interact with patho...

Full description

Autores:
Rodríguez Echeverri, Carolina
Gómez Giraldo, Beatriz Lucía
González Marín, Ángel Augusto
Tipo de recurso:
Article of investigation
Fecha de publicación:
2022
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/31486
Acceso en línea:
https://hdl.handle.net/10495/31486
https://www.mdpi.com/2309-608X/8/10/1108
Palabra clave:
Histoplasma
Receptor Toll-Like 2
Toll-Like Receptor 2
Células Madre Hematopoyéticas
Hematopoietic Stem Cells
Receptor Toll-Like 4
Toll-Like Receptor 4
Rights
openAccess
License
http://creativecommons.org/licenses/by/2.5/co/
id UDEA2_c6fd87da935469fb21195ef9080e9c2c
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/31486
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1
title Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1
spellingShingle Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1
Histoplasma
Receptor Toll-Like 2
Toll-Like Receptor 2
Células Madre Hematopoyéticas
Hematopoietic Stem Cells
Receptor Toll-Like 4
Toll-Like Receptor 4
title_short Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1
title_full Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1
title_fullStr Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1
title_full_unstemmed Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1
title_sort Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1
dc.creator.fl_str_mv Rodríguez Echeverri, Carolina
Gómez Giraldo, Beatriz Lucía
González Marín, Ángel Augusto
dc.contributor.author.none.fl_str_mv Rodríguez Echeverri, Carolina
Gómez Giraldo, Beatriz Lucía
González Marín, Ángel Augusto
dc.subject.decs.none.fl_str_mv Histoplasma
Receptor Toll-Like 2
Toll-Like Receptor 2
Células Madre Hematopoyéticas
Hematopoietic Stem Cells
Receptor Toll-Like 4
Toll-Like Receptor 4
topic Histoplasma
Receptor Toll-Like 2
Toll-Like Receptor 2
Células Madre Hematopoyéticas
Hematopoietic Stem Cells
Receptor Toll-Like 4
Toll-Like Receptor 4
description ABSTRACT: Hematopoietic stem cells (HSCs), a multipotent and self-renewing population responsible for the generation and maintenance of blood cells, have been the subject of numerous investigations due to their therapeutic potential. It has been shown that these cells are able to interact with pathogens through the TLRs that they express on their surface, affecting the hematopoiesis process. However, the interaction between hematopoietic stem and progenitor cells (HSPC) with fungal pathogens such as Histoplasma capsulatum has not been studied. Therefore, the objective of the present study was to determine if the interaction of HSPCs with H. capsulatum yeasts affects the hematopoiesis, activation, or proliferation of these cells. The results indicate that HSPCs are able to adhere to and internalize H. capsulatum yeasts through a mechanism dependent on TLR2, TLR4, and Dectin-1; however, this process does not affect the survival of the fungus, and, on the contrary, such interaction induces a significant increase in the expression of IL-1β, IL-6, IL-10, IL-17, TNF-α, and TGF-β, as well as the immune mediators Arg-1 and iNOS. Moreover, H. capsulatum induces apoptosis and alters HSPC proliferation. These findings suggest that H. capsulatum directly modulates the immune response exerted by HPSC through PRRs, and this interaction could directly affect the process of hematopoiesis, a fact that could explain clinical manifestations such as anemia and pancytopenia in patients with severe histoplasmosis, especially in those with fungal spread to the bone marrow
publishDate 2022
dc.date.accessioned.none.fl_str_mv 2022-10-27T12:59:20Z
dc.date.available.none.fl_str_mv 2022-10-27T12:59:20Z
dc.date.issued.none.fl_str_mv 2022
dc.type.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.hasversion.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.local.spa.fl_str_mv Artículo de investigación
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.citation.spa.fl_str_mv Rodríguez-Echeverri, C.; Gómez, B.L.; González, Á. Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1. J. Fungi 2022, 8, 1108. https://doi.org/10.3390/ jof8101108
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/31486
dc.identifier.doi.none.fl_str_mv 10.3390/jof8101108
dc.identifier.eissn.none.fl_str_mv 2309-608X
dc.identifier.url.spa.fl_str_mv https://www.mdpi.com/2309-608X/8/10/1108
identifier_str_mv Rodríguez-Echeverri, C.; Gómez, B.L.; González, Á. Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1. J. Fungi 2022, 8, 1108. https://doi.org/10.3390/ jof8101108
10.3390/jof8101108
2309-608X
url https://hdl.handle.net/10495/31486
https://www.mdpi.com/2309-608X/8/10/1108
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv J. Fungi.
dc.rights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by/2.5/co/
dc.rights.accessrights.spa.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.creativecommons.spa.fl_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/2.5/co/
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.format.extent.spa.fl_str_mv 12
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv MDPI (Multidisciplinary Digital Publishing Institute)
dc.publisher.group.spa.fl_str_mv Grupo de Investigación en Microbiología Básica y Aplicada-Microba
dc.publisher.place.spa.fl_str_mv Basilea, Suiza
institution Universidad de Antioquia
bitstream.url.fl_str_mv https://bibliotecadigital.udea.edu.co/bitstream/10495/31486/1/RodriguezCarolina_2022_HistoplasmaCapsulatumActivates.pdf
https://bibliotecadigital.udea.edu.co/bitstream/10495/31486/3/license.txt
https://bibliotecadigital.udea.edu.co/bitstream/10495/31486/2/license_rdf
bitstream.checksum.fl_str_mv ee5227eb615a1c9836b786e2db393d13
8a4605be74aa9ea9d79846c1fba20a33
1646d1f6b96dbbbc38035efc9239ac9c
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad de Antioquia
repository.mail.fl_str_mv andres.perez@udea.edu.co
_version_ 1812173112148492288
spelling Rodríguez Echeverri, CarolinaGómez Giraldo, Beatriz LucíaGonzález Marín, Ángel Augusto2022-10-27T12:59:20Z2022-10-27T12:59:20Z2022Rodríguez-Echeverri, C.; Gómez, B.L.; González, Á. Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1. J. Fungi 2022, 8, 1108. https://doi.org/10.3390/ jof8101108https://hdl.handle.net/10495/3148610.3390/jof81011082309-608Xhttps://www.mdpi.com/2309-608X/8/10/1108ABSTRACT: Hematopoietic stem cells (HSCs), a multipotent and self-renewing population responsible for the generation and maintenance of blood cells, have been the subject of numerous investigations due to their therapeutic potential. It has been shown that these cells are able to interact with pathogens through the TLRs that they express on their surface, affecting the hematopoiesis process. However, the interaction between hematopoietic stem and progenitor cells (HSPC) with fungal pathogens such as Histoplasma capsulatum has not been studied. Therefore, the objective of the present study was to determine if the interaction of HSPCs with H. capsulatum yeasts affects the hematopoiesis, activation, or proliferation of these cells. The results indicate that HSPCs are able to adhere to and internalize H. capsulatum yeasts through a mechanism dependent on TLR2, TLR4, and Dectin-1; however, this process does not affect the survival of the fungus, and, on the contrary, such interaction induces a significant increase in the expression of IL-1β, IL-6, IL-10, IL-17, TNF-α, and TGF-β, as well as the immune mediators Arg-1 and iNOS. Moreover, H. capsulatum induces apoptosis and alters HSPC proliferation. These findings suggest that H. capsulatum directly modulates the immune response exerted by HPSC through PRRs, and this interaction could directly affect the process of hematopoiesis, a fact that could explain clinical manifestations such as anemia and pancytopenia in patients with severe histoplasmosis, especially in those with fungal spread to the bone marrowCOL012613112application/pdfengMDPI (Multidisciplinary Digital Publishing Institute)Grupo de Investigación en Microbiología Básica y Aplicada-MicrobaBasilea, Suizainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/co/http://purl.org/coar/access_right/c_abf2https://creativecommons.org/licenses/by/4.0/Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1HistoplasmaReceptor Toll-Like 2Toll-Like Receptor 2Células Madre HematopoyéticasHematopoietic Stem CellsReceptor Toll-Like 4Toll-Like Receptor 4J. Fungi.Journal of Fungi112810ORIGINALRodriguezCarolina_2022_HistoplasmaCapsulatumActivates.pdfRodriguezCarolina_2022_HistoplasmaCapsulatumActivates.pdfArtículo de investigaciónapplication/pdf2058408https://bibliotecadigital.udea.edu.co/bitstream/10495/31486/1/RodriguezCarolina_2022_HistoplasmaCapsulatumActivates.pdfee5227eb615a1c9836b786e2db393d13MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstream/10495/31486/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8927https://bibliotecadigital.udea.edu.co/bitstream/10495/31486/2/license_rdf1646d1f6b96dbbbc38035efc9239ac9cMD5210495/31486oai:bibliotecadigital.udea.edu.co:10495/314862022-10-27 07:59:21.905Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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