title: Mucosal Th17 cell function is altered during HIV infection and is an independent predictor of systemic immune activation.
abstract: Mucosal Th17 cells maintain the gut epithelial barrier and prevent invasion by luminal bacteria through a delicate balance of immunosuppressive and proinflammatory functions. HIV infection is characterized by mucosal Th17 depletion, microbial translocation, and immune activation. Therefore, we assessed the function of blood and sigmoid Th17 cells during both early and chronic HIV infection, as well as the impact of short- and long-term antiretroviral therapy. Th17 cells were defined as IL-17a(+) CD4 T cells, and their functional capacity was assessed by the coproduction of the inflammatory cytokines IL-22, TNF-α, and IFN-γ, as well as the immunoregulatory cytokine IL-10. Gut Th17 cells had a much greater capacity to produce proinflammatory cytokines than did those from the blood, but this capacity was dramatically reduced from the earliest stages of HIV infection. Immunoregulatory skewing of mucosal Th17 cell function, characterized by an increased IL-10/TNF-α ratio, was uniquely seen during early HIV infection and was independently associated with reduced systemic immune activation. Antiretroviral therapy rapidly restored mucosal Th17 cell numbers; however, normalization of mucosal Th17 function, microbial translocation, and mucosal/systemic immune activation was much delayed. These findings emphasize that strategies to preserve or to more rapidly restore mucosal Th17 function may have important therapeutic benefit.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Kim
authors.forename: Lyle R
authors.initials: LR
authors.lastname: McKinnon
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.forename: Gabor
authors.initials: G
authors.lastname: Kandel
authors.forename: Sanja
authors.initials: S
authors.lastname: Huibner
authors.forename: Duncan
authors.initials: D
authors.lastname: Chege
authors.forename: Kamnoosh
authors.initials: K
authors.lastname: Shahabi
authors.forename: Erika
authors.initials: E
authors.lastname: Benko
authors.forename: Mona
authors.initials: M
authors.lastname: Loutfy
authors.forename: Mario
authors.initials: M
authors.lastname: Ostrowski
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents