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Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunol...

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Autores principales: Liu, Fengliang, Fan, Xiuzhen, Auclair, Sarah, Ferguson, Monique, Sun, Jiaren, Soong, Lynn, Hou, Wei, Redfield, Robert R., Birx, Deborah L., Ratto-Kim, Silvia, Robb, Merlin L., Kim, Jerome H., Michael, Nelson L., Hu, Haitao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900544/
https://www.ncbi.nlm.nih.gov/pubmed/27280548
http://dx.doi.org/10.1371/journal.ppat.1005663
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author Liu, Fengliang
Fan, Xiuzhen
Auclair, Sarah
Ferguson, Monique
Sun, Jiaren
Soong, Lynn
Hou, Wei
Redfield, Robert R.
Birx, Deborah L.
Ratto-Kim, Silvia
Robb, Merlin L.
Kim, Jerome H.
Michael, Nelson L.
Hu, Haitao
author_facet Liu, Fengliang
Fan, Xiuzhen
Auclair, Sarah
Ferguson, Monique
Sun, Jiaren
Soong, Lynn
Hou, Wei
Redfield, Robert R.
Birx, Deborah L.
Ratto-Kim, Silvia
Robb, Merlin L.
Kim, Jerome H.
Michael, Nelson L.
Hu, Haitao
author_sort Liu, Fengliang
collection PubMed
description Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis.
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spelling pubmed-49005442016-06-24 Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection Liu, Fengliang Fan, Xiuzhen Auclair, Sarah Ferguson, Monique Sun, Jiaren Soong, Lynn Hou, Wei Redfield, Robert R. Birx, Deborah L. Ratto-Kim, Silvia Robb, Merlin L. Kim, Jerome H. Michael, Nelson L. Hu, Haitao PLoS Pathog Research Article Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. Public Library of Science 2016-06-09 /pmc/articles/PMC4900544/ /pubmed/27280548 http://dx.doi.org/10.1371/journal.ppat.1005663 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Liu, Fengliang
Fan, Xiuzhen
Auclair, Sarah
Ferguson, Monique
Sun, Jiaren
Soong, Lynn
Hou, Wei
Redfield, Robert R.
Birx, Deborah L.
Ratto-Kim, Silvia
Robb, Merlin L.
Kim, Jerome H.
Michael, Nelson L.
Hu, Haitao
Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection
title Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection
title_full Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection
title_fullStr Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection
title_full_unstemmed Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection
title_short Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection
title_sort sequential dysfunction and progressive depletion of candida albicans-specific cd4 t cell response in hiv-1 infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900544/
https://www.ncbi.nlm.nih.gov/pubmed/27280548
http://dx.doi.org/10.1371/journal.ppat.1005663
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