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Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

Damouche A, Lazure T, Avettand-Fènoël V, Huot N, Dejucq-Rainsford N, Satie AP, Mélard A, David L, Gommet C, Ghosn J, Noel N, Pourcher G, Martinez V, Benoist S, Béréziat V, Cosma A, Favier B, Vaslin B, Rouzioux C, Capeau J, Müller-Trutwin M, Dereuddre-Bosquet N, Le Grand R, Lambotte O, Bourgeois C - PLoS Pathog. (2015)

Bottom Line: We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue.Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue.These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways.

View Article: PubMed Central - PubMed

Affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.

ABSTRACT
Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways.

No MeSH data available.


Related in: MedlinePlus

The influence of SIV infection on adipose-resident T cell subsets.(A) Percentages and numbers (expressed per gram of adipose tissue recovered) of CD3-expressing cells among the CD45+ fraction from SCAT and VAT in non-infected animals (open circles) and SIV-infected animals (filled squares). Percentages were derived for 12 to 13 animals per group and counts were derived for 8 to 12 animals. (B) Representative dot plots showing CD4 and CD8 expression among CD3+ T cells in SIV-infected and non-infected animals. (C) Percentages and numbers (expressed per gram of adipose tissue) of CD4- and CD8-expressing cells among CD3+ cells recovered from SCAT and VAT of non-infected animals (open circles) and SIV-infected animals (filled squares). Percentages were derived for 8 to 12 animals per group and counts were derived for 5 to 8 animals. Data are quoted as the median [interquartile range]. Significant differences in a Mann-Whitney non-parametric test are shown as * p<0.05; ** p<0.01; *** p<0.001.
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ppat.1005153.g002: The influence of SIV infection on adipose-resident T cell subsets.(A) Percentages and numbers (expressed per gram of adipose tissue recovered) of CD3-expressing cells among the CD45+ fraction from SCAT and VAT in non-infected animals (open circles) and SIV-infected animals (filled squares). Percentages were derived for 12 to 13 animals per group and counts were derived for 8 to 12 animals. (B) Representative dot plots showing CD4 and CD8 expression among CD3+ T cells in SIV-infected and non-infected animals. (C) Percentages and numbers (expressed per gram of adipose tissue) of CD4- and CD8-expressing cells among CD3+ cells recovered from SCAT and VAT of non-infected animals (open circles) and SIV-infected animals (filled squares). Percentages were derived for 8 to 12 animals per group and counts were derived for 5 to 8 animals. Data are quoted as the median [interquartile range]. Significant differences in a Mann-Whitney non-parametric test are shown as * p<0.05; ** p<0.01; *** p<0.001.

Mentions: We next looked at whether or not SIV infection was associated with changes in the percentages of CD4+ and CD8+ T lymphocytes within adipose tissue. To this end, we determined the percentage of total T lymphocytes among CD45-expressing cells and the percentages of CD4+ and CD8+ T lymphocytes among CD3-expressing cells (Fig 2). Adipose tissue T lymphocytes accounted for approximately half of the CD45+ cells within the SVF; SIV-infected and non-infected animals did not differ significantly in terms of the proportion and number of CD3+ cells (Fig 2A).


Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

Damouche A, Lazure T, Avettand-Fènoël V, Huot N, Dejucq-Rainsford N, Satie AP, Mélard A, David L, Gommet C, Ghosn J, Noel N, Pourcher G, Martinez V, Benoist S, Béréziat V, Cosma A, Favier B, Vaslin B, Rouzioux C, Capeau J, Müller-Trutwin M, Dereuddre-Bosquet N, Le Grand R, Lambotte O, Bourgeois C - PLoS Pathog. (2015)

The influence of SIV infection on adipose-resident T cell subsets.(A) Percentages and numbers (expressed per gram of adipose tissue recovered) of CD3-expressing cells among the CD45+ fraction from SCAT and VAT in non-infected animals (open circles) and SIV-infected animals (filled squares). Percentages were derived for 12 to 13 animals per group and counts were derived for 8 to 12 animals. (B) Representative dot plots showing CD4 and CD8 expression among CD3+ T cells in SIV-infected and non-infected animals. (C) Percentages and numbers (expressed per gram of adipose tissue) of CD4- and CD8-expressing cells among CD3+ cells recovered from SCAT and VAT of non-infected animals (open circles) and SIV-infected animals (filled squares). Percentages were derived for 8 to 12 animals per group and counts were derived for 5 to 8 animals. Data are quoted as the median [interquartile range]. Significant differences in a Mann-Whitney non-parametric test are shown as * p<0.05; ** p<0.01; *** p<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581628&req=5

ppat.1005153.g002: The influence of SIV infection on adipose-resident T cell subsets.(A) Percentages and numbers (expressed per gram of adipose tissue recovered) of CD3-expressing cells among the CD45+ fraction from SCAT and VAT in non-infected animals (open circles) and SIV-infected animals (filled squares). Percentages were derived for 12 to 13 animals per group and counts were derived for 8 to 12 animals. (B) Representative dot plots showing CD4 and CD8 expression among CD3+ T cells in SIV-infected and non-infected animals. (C) Percentages and numbers (expressed per gram of adipose tissue) of CD4- and CD8-expressing cells among CD3+ cells recovered from SCAT and VAT of non-infected animals (open circles) and SIV-infected animals (filled squares). Percentages were derived for 8 to 12 animals per group and counts were derived for 5 to 8 animals. Data are quoted as the median [interquartile range]. Significant differences in a Mann-Whitney non-parametric test are shown as * p<0.05; ** p<0.01; *** p<0.001.
Mentions: We next looked at whether or not SIV infection was associated with changes in the percentages of CD4+ and CD8+ T lymphocytes within adipose tissue. To this end, we determined the percentage of total T lymphocytes among CD45-expressing cells and the percentages of CD4+ and CD8+ T lymphocytes among CD3-expressing cells (Fig 2). Adipose tissue T lymphocytes accounted for approximately half of the CD45+ cells within the SVF; SIV-infected and non-infected animals did not differ significantly in terms of the proportion and number of CD3+ cells (Fig 2A).

Bottom Line: We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue.Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue.These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways.

View Article: PubMed Central - PubMed

Affiliation: Université Paris Sud, UMR 1184, Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France.

ABSTRACT
Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways.

No MeSH data available.


Related in: MedlinePlus