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Mucosal cell populations may contribute to peripheral immune abnormalities in HIV-infected subjects introducing cART with moderate immune-suppression.
- Source :
-
PloS one [PLoS One] 2019 Feb 14; Vol. 14 (2), pp. e0212075. Date of Electronic Publication: 2019 Feb 14 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- HIV infection causes the progressive depletion of CD4+ T-lymphocytes and profound modifications of T-cell homeostasis, which persist despite virologically-suppressive treatment and have been linked to a worse clinical outcome. Enduring alterations of the gastrointestinal tract may represent the underlying pathogenic mechanisms of these phenomena. Twenty-six HIV-infected subjects were assessed over a 12-month period following the introduction of antiretroviral therapy. 18 uninfected individuals were enrolled as controls. Parameters of peripheral T-cell homeostasis (activation, maturation), gastrointestinal function (microbial translocation, gut inflammation, fecal microbiota composition) and mucosal immunity (CD4+CCR6+CD161+, CD4+CCR9+α4β7+, stem cell memory CD4+/CD8+ T-cells) were assessed. CD4+CCR6+CD161+ cells were depleted in HIV-infected untreated subjects and maintained significantly lower levels compared to controls, despite the introduction of effective antiviral treatment. The frequency of gut-homing CD4+CCR9+α4β7+ cells was also impaired in untreated infection and correlated with the HIV RNA load and CD4+HLADR+CD38+; during therapy, we observed a contraction of this pool in the peripheral blood and the loss of its correlation with antigenic exposure/immune activation. A partial correction of the balance between stem cell memory pools and T-cell homeostasis was registered following treatment. In HIV-infected subjects with moderate immune-suppression, antiretroviral therapy has a marginal impact on mucosal immune populations which feature distinctive kinetics in the periphery, possibly reflecting their diverse recruitment from the blood to the mucosa. The persistent defects in mucosal immunity may fuel peripheral T-cell abnormalities through diverse mechanisms, including the production of IL-17/IL-22, cellular permissiveness to infection and regulation of T-lymphocyte maturation.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Adult
Anti-HIV Agents pharmacology
Drug Interactions
Feces microbiology
Female
Gastrointestinal Tract drug effects
Gastrointestinal Tract immunology
Gastrointestinal Tract microbiology
HIV Infections microbiology
Humans
Male
Microbiota drug effects
Middle Aged
T-Lymphocytes drug effects
T-Lymphocytes immunology
Anti-HIV Agents therapeutic use
HIV Infections drug therapy
HIV Infections immunology
Immune Tolerance
Immunity, Mucosal drug effects
Mucous Membrane cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 14
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 30763359
- Full Text :
- https://doi.org/10.1371/journal.pone.0212075