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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Mucosal Th17 cell function is altered during HIV infection and is an independent predictor of systemic immune activation
Journal of Immunology, Volume 191, No. 5, Year 2013
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Description
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. Copyright © 2013 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Kim, Connie J.
Canada, Toronto
University of Toronto
McKinnon, Lyle R.
Canada, Toronto
University of Toronto
Kenya, Nairobi
University of Nairobi
Kovacs, Colin M.
Canada, Toronto
Maple Leaf Medical Clinic
Kandel, Gabor
Canada, Toronto
University of Toronto
Canada, Toronto
Saint Michael's Hospital University of Toronto
Huibner, Sanja
Canada, Toronto
University of Toronto
Chege, Duncan
Canada, Toronto
University of Toronto
Shahabi, Kamnoosh
Canada, Toronto
University of Toronto
Benko, Erika
Canada, Toronto
Maple Leaf Medical Clinic
Loutfy, Mona
Canada, Toronto
University of Toronto
Canada, Toronto
Maple Leaf Medical Clinic
Canada, Toronto
Women's College Hospital
Ostrowski, Mario A.
Canada, Toronto
University of Toronto
Canada, Toronto
Saint Michael's Hospital University of Toronto
Kaul, Rupert
Canada, Toronto
University of Toronto
Canada, Toronto
University Health Network University of Toronto
Statistics
Citations: 109
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.4049/jimmunol.1300829
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Infectious Diseases