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Fecal Microbiota Composition Drives Immune Activation in HIV-infected Individuals

The inflammatory properties of the enteric microbiota of Human Immunodeficiency Virus (HIV)-infected individuals are of considerable interest because of strong evidence that bacterial translocation contributes to chronic immune activation and disease progression. Altered enteric microbiota compositi...

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Autores principales: Neff, Charles Preston, Krueger, Owen, Xiong, Kathy, Arif, Sabrina, Nusbacher, Nichole, Schneider, Jennifer M., Cunningham, Annie W., Armstrong, Abigail, Li, Sam, McCarter, Martin D., Campbell, Thomas B., Lozupone, Catherine A., Palmer, Brent E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952409/
https://www.ncbi.nlm.nih.gov/pubmed/29650491
http://dx.doi.org/10.1016/j.ebiom.2018.03.024
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author Neff, Charles Preston
Krueger, Owen
Xiong, Kathy
Arif, Sabrina
Nusbacher, Nichole
Schneider, Jennifer M.
Cunningham, Annie W.
Armstrong, Abigail
Li, Sam
McCarter, Martin D.
Campbell, Thomas B.
Lozupone, Catherine A.
Palmer, Brent E.
author_facet Neff, Charles Preston
Krueger, Owen
Xiong, Kathy
Arif, Sabrina
Nusbacher, Nichole
Schneider, Jennifer M.
Cunningham, Annie W.
Armstrong, Abigail
Li, Sam
McCarter, Martin D.
Campbell, Thomas B.
Lozupone, Catherine A.
Palmer, Brent E.
author_sort Neff, Charles Preston
collection PubMed
description The inflammatory properties of the enteric microbiota of Human Immunodeficiency Virus (HIV)-infected individuals are of considerable interest because of strong evidence that bacterial translocation contributes to chronic immune activation and disease progression. Altered enteric microbiota composition occurs with HIV infection but whether altered microbiota composition or increased intestinal permeability alone drives peripheral immune activation is controversial. To comprehensively assess the inflammatory properties of HIV-associated enteric microbiota and relate these to systemic immune activation, we developed methods to purify whole fecal bacterial communities (FBCs) from stool for use in in vitro immune stimulation assays with human cells. We show that the enteric microbiota of untreated HIV-infected subjects induce significantly higher levels of activated monocytes and T cells compared to seronegative subjects. FBCs from anti-retroviral therapy (ART)-treated HIV-infected individuals induced intermediate T cell activation, indicating an only partial correction of adaptive immune cell activation capacity of the microbiome with ART. In vitro activation levels correlated with activation levels and viral load in blood and were particularly high in individuals harboring specific gram-positive opportunistic pathogens. Blockade experiments implicated Tumor Necrosis Factor (TNF)-α and Toll-Like Receptor-2 (TLR2), which recognizes peptidoglycan, as strong mediators of T cell activation; This may contradict a previous focus on lipopolysaccharide as a primary mediator of chronic immune activation. These data support that increased inflammatory properties of the enteric microbiota and not increased permeability alone drives chronic inflammation in HIV.
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spelling pubmed-59524092018-05-16 Fecal Microbiota Composition Drives Immune Activation in HIV-infected Individuals Neff, Charles Preston Krueger, Owen Xiong, Kathy Arif, Sabrina Nusbacher, Nichole Schneider, Jennifer M. Cunningham, Annie W. Armstrong, Abigail Li, Sam McCarter, Martin D. Campbell, Thomas B. Lozupone, Catherine A. Palmer, Brent E. EBioMedicine Research Paper The inflammatory properties of the enteric microbiota of Human Immunodeficiency Virus (HIV)-infected individuals are of considerable interest because of strong evidence that bacterial translocation contributes to chronic immune activation and disease progression. Altered enteric microbiota composition occurs with HIV infection but whether altered microbiota composition or increased intestinal permeability alone drives peripheral immune activation is controversial. To comprehensively assess the inflammatory properties of HIV-associated enteric microbiota and relate these to systemic immune activation, we developed methods to purify whole fecal bacterial communities (FBCs) from stool for use in in vitro immune stimulation assays with human cells. We show that the enteric microbiota of untreated HIV-infected subjects induce significantly higher levels of activated monocytes and T cells compared to seronegative subjects. FBCs from anti-retroviral therapy (ART)-treated HIV-infected individuals induced intermediate T cell activation, indicating an only partial correction of adaptive immune cell activation capacity of the microbiome with ART. In vitro activation levels correlated with activation levels and viral load in blood and were particularly high in individuals harboring specific gram-positive opportunistic pathogens. Blockade experiments implicated Tumor Necrosis Factor (TNF)-α and Toll-Like Receptor-2 (TLR2), which recognizes peptidoglycan, as strong mediators of T cell activation; This may contradict a previous focus on lipopolysaccharide as a primary mediator of chronic immune activation. These data support that increased inflammatory properties of the enteric microbiota and not increased permeability alone drives chronic inflammation in HIV. Elsevier 2018-03-26 /pmc/articles/PMC5952409/ /pubmed/29650491 http://dx.doi.org/10.1016/j.ebiom.2018.03.024 Text en © 2018 German Center for Neurodegenerative Diseases (DZNE) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Neff, Charles Preston
Krueger, Owen
Xiong, Kathy
Arif, Sabrina
Nusbacher, Nichole
Schneider, Jennifer M.
Cunningham, Annie W.
Armstrong, Abigail
Li, Sam
McCarter, Martin D.
Campbell, Thomas B.
Lozupone, Catherine A.
Palmer, Brent E.
Fecal Microbiota Composition Drives Immune Activation in HIV-infected Individuals
title Fecal Microbiota Composition Drives Immune Activation in HIV-infected Individuals
title_full Fecal Microbiota Composition Drives Immune Activation in HIV-infected Individuals
title_fullStr Fecal Microbiota Composition Drives Immune Activation in HIV-infected Individuals
title_full_unstemmed Fecal Microbiota Composition Drives Immune Activation in HIV-infected Individuals
title_short Fecal Microbiota Composition Drives Immune Activation in HIV-infected Individuals
title_sort fecal microbiota composition drives immune activation in hiv-infected individuals
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952409/
https://www.ncbi.nlm.nih.gov/pubmed/29650491
http://dx.doi.org/10.1016/j.ebiom.2018.03.024
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