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Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients

Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementi...

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Autores principales: Ancuta, Petronela, Kamat, Anupa, Kunstman, Kevin J., Kim, Eun-Young, Autissier, Patrick, Wurcel, Alysse, Zaman, Tauheed, Stone, David, Mefford, Megan, Morgello, Susan, Singer, Elyse J., Wolinsky, Steven M., Gabuzda, Dana
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2424175/
https://www.ncbi.nlm.nih.gov/pubmed/18575590
http://dx.doi.org/10.1371/journal.pone.0002516
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author Ancuta, Petronela
Kamat, Anupa
Kunstman, Kevin J.
Kim, Eun-Young
Autissier, Patrick
Wurcel, Alysse
Zaman, Tauheed
Stone, David
Mefford, Megan
Morgello, Susan
Singer, Elyse J.
Wolinsky, Steven M.
Gabuzda, Dana
author_facet Ancuta, Petronela
Kamat, Anupa
Kunstman, Kevin J.
Kim, Eun-Young
Autissier, Patrick
Wurcel, Alysse
Zaman, Tauheed
Stone, David
Mefford, Megan
Morgello, Susan
Singer, Elyse J.
Wolinsky, Steven M.
Gabuzda, Dana
author_sort Ancuta, Petronela
collection PubMed
description Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4(+) T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes.
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spelling pubmed-24241752008-06-25 Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients Ancuta, Petronela Kamat, Anupa Kunstman, Kevin J. Kim, Eun-Young Autissier, Patrick Wurcel, Alysse Zaman, Tauheed Stone, David Mefford, Megan Morgello, Susan Singer, Elyse J. Wolinsky, Steven M. Gabuzda, Dana PLoS One Research Article Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4(+) T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes. Public Library of Science 2008-06-25 /pmc/articles/PMC2424175/ /pubmed/18575590 http://dx.doi.org/10.1371/journal.pone.0002516 Text en Ancuta et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ancuta, Petronela
Kamat, Anupa
Kunstman, Kevin J.
Kim, Eun-Young
Autissier, Patrick
Wurcel, Alysse
Zaman, Tauheed
Stone, David
Mefford, Megan
Morgello, Susan
Singer, Elyse J.
Wolinsky, Steven M.
Gabuzda, Dana
Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients
title Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients
title_full Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients
title_fullStr Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients
title_full_unstemmed Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients
title_short Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients
title_sort microbial translocation is associated with increased monocyte activation and dementia in aids patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2424175/
https://www.ncbi.nlm.nih.gov/pubmed/18575590
http://dx.doi.org/10.1371/journal.pone.0002516
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