HIV replication is associated to inflammasomes activation, IL-1, IL-18 and caspase-1 expression in GALT and peripheral blood

Background Human immunodeficiency virus (HIV) promotes an inflammatory process, leading to the progressive loss of the functional capacity of the immune system. The HIV infection induces alterations in several tissues, but mainly in the gut-associated lymphoid tissue (GALT). However, the degree of G...

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Autores:
Feria Garzón, Manuel Gerónimo
Taborda, Natalia Andrea
Hernández López, Juan Carlos
Rugeles López, María Teresa
Tipo de recurso:
Article of journal
Fecha de publicación:
2018
Institución:
Universidad Cooperativa de Colombia
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Repositorio UCC
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oai:repository.ucc.edu.co:20.500.12494/15591
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https://hdl.handle.net/20.500.12494/15591
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HIV
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openAccess
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oai_identifier_str oai:repository.ucc.edu.co:20.500.12494/15591
network_acronym_str COOPER2
network_name_str Repositorio UCC
repository_id_str
dc.title.spa.fl_str_mv HIV replication is associated to inflammasomes activation, IL-1, IL-18 and caspase-1 expression in GALT and peripheral blood
title HIV replication is associated to inflammasomes activation, IL-1, IL-18 and caspase-1 expression in GALT and peripheral blood
spellingShingle HIV replication is associated to inflammasomes activation, IL-1, IL-18 and caspase-1 expression in GALT and peripheral blood
HIV
title_short HIV replication is associated to inflammasomes activation, IL-1, IL-18 and caspase-1 expression in GALT and peripheral blood
title_full HIV replication is associated to inflammasomes activation, IL-1, IL-18 and caspase-1 expression in GALT and peripheral blood
title_fullStr HIV replication is associated to inflammasomes activation, IL-1, IL-18 and caspase-1 expression in GALT and peripheral blood
title_full_unstemmed HIV replication is associated to inflammasomes activation, IL-1, IL-18 and caspase-1 expression in GALT and peripheral blood
title_sort HIV replication is associated to inflammasomes activation, IL-1, IL-18 and caspase-1 expression in GALT and peripheral blood
dc.creator.fl_str_mv Feria Garzón, Manuel Gerónimo
Taborda, Natalia Andrea
Hernández López, Juan Carlos
Rugeles López, María Teresa
dc.contributor.author.none.fl_str_mv Feria Garzón, Manuel Gerónimo
Taborda, Natalia Andrea
Hernández López, Juan Carlos
Rugeles López, María Teresa
dc.subject.spa.fl_str_mv HIV
topic HIV
description Background Human immunodeficiency virus (HIV) promotes an inflammatory process, leading to the progressive loss of the functional capacity of the immune system. The HIV infection induces alterations in several tissues, but mainly in the gut-associated lymphoid tissue (GALT). However, the degree of GALT deterioration varies among infected individuals. In fact, it has been shown that HIV-controllers, who spontaneously control viral replication, exhibit a lower inflammatory response, and a relative normal frequency and function of most of the immune cells. Inflammasomes are molecular complexes involved in the inflammatory response, being NLRP1, NLRP3, NLRC4, AIM2 and Pyrin inflammasomes, the best characterized so far. These complexes regulate the maturation of cytokines of the IL-1 family, including IL-1β and IL-18. These cytokines have been associated with immune activation and expansion of HIV target cells, promoting viral replication. Interesting, some reports indicate that HIV induces the activation of the NLRP3 inflammasome, but the role of this, and other inflammasomes during HIV infection, especially in GALT, remains unclear. Objective To compare the relative expression of inflammasome components and the proinflammatory response related to their activity, between HIV-progressors and HIV-controllers.Methods GALT biopsies and peripheral blood mononuclear cells (PBMCs) from 15 HIV-controllers and 15 HIV-progressors were obtained. The relative expression of the following inflammasome components were evaluated by RT-PCR: NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1β and IL-18. In addition, plasma concentration of IL-18 was evaluated as an indicator of baseline proinflammatory status. Finally, in supernatants of PBMCs in vitro stimulated with inflammasome agonists, the concentrations of IL-1β and IL-18 were quantified by ELISA. Results HIV-progressors exhibited higher expression of IL-1β, IL-18 and caspase-1 genes in GALT and PBMCs compared with HIV-controllers. In addition, HIV-progressors had also increased expression of ASC in PBMCs. When plasma levels were evaluated, IL-18 was increased in HIV-progressors. Interesting, these patients also showed an increased production of IL-1β in supernatants of PBMCs stimulated in vitro with the agonists of AIM2, NLRP1 and NLRC4 inflammasomes. Finally, the expression of caspase-1, NLRP1, IL-1β and IL-18 in GALT or peripheral blood was correlated with CD4+ T-cell count and viral load. Conclusion Our results suggest that during HIV-infection, the required signals to induce the expression of different components of the inflammasomes are produced, both in GALT and in periphery. The activation of these molecular complexes could increase the number of target cells, favoring HIV replication and cell death, promoting the disease progression.
publishDate 2018
dc.date.issued.none.fl_str_mv 2018-04-19
dc.date.accessioned.none.fl_str_mv 2019-12-12T15:10:08Z
dc.date.available.none.fl_str_mv 2019-12-12T15:10:08Z
dc.type.none.fl_str_mv Artículo
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dc.identifier.issn.spa.fl_str_mv 1932-6203
dc.identifier.uri.spa.fl_str_mv 10.1371/journal.pone.0192845
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dc.identifier.bibliographicCitation.spa.fl_str_mv Feria MG, Taborda NA, Hernandez JC, Rugeles MT (2018) HIV replication is associated to inflammasomes activation, IL-1β, IL-18 and caspase-1 expression in GALT and peripheral blood. PLoS ONE 13(4): e0192845. https://doi.org/ 10.1371/journal.pone.0192845. Recuperado de:
identifier_str_mv 1932-6203
10.1371/journal.pone.0192845
Feria MG, Taborda NA, Hernandez JC, Rugeles MT (2018) HIV replication is associated to inflammasomes activation, IL-1β, IL-18 and caspase-1 expression in GALT and peripheral blood. PLoS ONE 13(4): e0192845. https://doi.org/ 10.1371/journal.pone.0192845. Recuperado de:
url https://hdl.handle.net/20.500.12494/15591
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dc.relation.ispartofjournal.spa.fl_str_mv PLOS ONE
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spelling Feria Garzón, Manuel GerónimoTaborda, Natalia AndreaHernández López, Juan CarlosRugeles López, María Teresa13 (4)2019-12-12T15:10:08Z2019-12-12T15:10:08Z2018-04-191932-620310.1371/journal.pone.0192845https://hdl.handle.net/20.500.12494/15591Feria MG, Taborda NA, Hernandez JC, Rugeles MT (2018) HIV replication is associated to inflammasomes activation, IL-1β, IL-18 and caspase-1 expression in GALT and peripheral blood. PLoS ONE 13(4): e0192845. https://doi.org/ 10.1371/journal.pone.0192845. Recuperado de:Background Human immunodeficiency virus (HIV) promotes an inflammatory process, leading to the progressive loss of the functional capacity of the immune system. The HIV infection induces alterations in several tissues, but mainly in the gut-associated lymphoid tissue (GALT). However, the degree of GALT deterioration varies among infected individuals. In fact, it has been shown that HIV-controllers, who spontaneously control viral replication, exhibit a lower inflammatory response, and a relative normal frequency and function of most of the immune cells. Inflammasomes are molecular complexes involved in the inflammatory response, being NLRP1, NLRP3, NLRC4, AIM2 and Pyrin inflammasomes, the best characterized so far. These complexes regulate the maturation of cytokines of the IL-1 family, including IL-1β and IL-18. These cytokines have been associated with immune activation and expansion of HIV target cells, promoting viral replication. Interesting, some reports indicate that HIV induces the activation of the NLRP3 inflammasome, but the role of this, and other inflammasomes during HIV infection, especially in GALT, remains unclear. Objective To compare the relative expression of inflammasome components and the proinflammatory response related to their activity, between HIV-progressors and HIV-controllers.Methods GALT biopsies and peripheral blood mononuclear cells (PBMCs) from 15 HIV-controllers and 15 HIV-progressors were obtained. The relative expression of the following inflammasome components were evaluated by RT-PCR: NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1β and IL-18. In addition, plasma concentration of IL-18 was evaluated as an indicator of baseline proinflammatory status. Finally, in supernatants of PBMCs in vitro stimulated with inflammasome agonists, the concentrations of IL-1β and IL-18 were quantified by ELISA. Results HIV-progressors exhibited higher expression of IL-1β, IL-18 and caspase-1 genes in GALT and PBMCs compared with HIV-controllers. In addition, HIV-progressors had also increased expression of ASC in PBMCs. When plasma levels were evaluated, IL-18 was increased in HIV-progressors. Interesting, these patients also showed an increased production of IL-1β in supernatants of PBMCs stimulated in vitro with the agonists of AIM2, NLRP1 and NLRC4 inflammasomes. Finally, the expression of caspase-1, NLRP1, IL-1β and IL-18 in GALT or peripheral blood was correlated with CD4+ T-cell count and viral load. Conclusion Our results suggest that during HIV-infection, the required signals to induce the expression of different components of the inflammasomes are produced, both in GALT and in periphery. 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Nat Immunol. 2013; 14(12):1207–8. https://doi.org/10.1038/ni.2763 PMID: 24240152HIVHIV replication is associated to inflammasomes activation, IL-1, IL-18 and caspase-1 expression in GALT and peripheral bloodArtículohttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAtribucióninfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2PublicationLICENSElicense.txtlicense.txttext/plain; charset=utf-84334https://repository.ucc.edu.co/bitstreams/4e00d63b-bb8b-4aa7-955a-ce09b2dbfff1/download3bce4f7ab09dfc588f126e1e36e98a45MD52ORIGINALInflammasome HIV GALT 2018 PLoS ONE.pdfInflammasome HIV GALT 2018 PLoS ONE.pdfapplication/pdf1433558https://repository.ucc.edu.co/bitstreams/49ce275e-9f95-4a72-a2ec-bf0d32b8f8cc/download20ad426c5c592568ea6495f567aeafc2MD51TEXTInflammasome HIV GALT 2018 PLoS ONE.pdf.txtInflammasome HIV GALT 2018 PLoS 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