Th17 cells, HIV and the gut mucosal barrier

We will present recent studies on a subset of CD4 T helper cells, Th17 cells, that appears to be critical for regulating gut mucosal immune responses against extracellular microbial pathogens and may serve as a link between innate and adaptive immune responses. Implications of the loss of Th17 CD4 T cells in HIV infection will be discussed in relation to the chronic immune activation and HIV pathogenesis.

Severe depletion of CD4 T cells occurs in the gut mucosa during primary HIV and simian immunodeficiency virus infections. A pronounced loss of mucosal Th17 CD4 T cells in the simian immunodeficiency virus-infected rhesus macaque model of AIDS is linked to impaired immune responses in the gut mucosa to an enteric pathogen, Salmonella typhimurium, leading to the lack of local control of the pathogen and its translocation. Recovery of the gut mucosal immune system during highly active antiretroviral therapy is slow and incomplete compared with the peripheral blood compartment. Recent studies suggest that the replenishment of Th17 CD4 T cells in the gut mucosa during highly active antiretroviral therapy, or during nonpathogenic simian immunodeficiency virus infections in the nonhuman primate models, correlates with better restoration and function of the gut mucosal immune system.

A better understanding of the role of Th17 CD4 cells in the generation of mucosal immune responses to enteric pathogens and maintenance of the intestinal epithelial integrity in HIV-infected patients will help in the development of novel strategies to modulate and enhance mucosal immune system and its function.