β-defensins that bind CCR6: Blunting the permissiveness of Th17 cells to HIV infection (P4432)

Abstract

Abstract HIV preferentially depletes IL-17-producing, CD4+ “T helper 17” (Th17) cells from the gut during the acute phase of infection. Th17 cells play a key role in mucosal barrier maintenance and protection against opportunistic infections commonly associated with HIV/AIDS. In response to IL-17, epithelial cells of mucosal barriers secrete β-defensins - a family of secreted, cationic peptides with potent broad-range antimicrobial activity against bacteria, fungi, and viruses including HIV. Our laboratory has shown that the expression of human β-defensin 2 (hBD2) is markedly decreased in the oral mucosa of HIV+ subjects, and that β-defensins, in addition to direct antimicrobial activity, upregulate the HIV restriction factor APOBEC3G via the chemokine receptor CCR6, which is expressed on Th17 cells. In order to characterize the effects of HIV infection on the Th17 subset and determine if β-defensins can protect Th17 cells from HIV infection, activated human primary CD4+ T cells are infected and/or treated with β-defensin, then characterized by flow cytometry. Our results show that IL-17A+ cells from peripheral blood are highly permissive to HIV, and are preferentially lost during infection. In addition, our model suggests that Th17-polarizing cytokines enhance HIV infection, and that β-defensins can protect these cells from infection. Our studies of the factors contributing to protection of Th17 cells may yield new therapeutic targets to protect the Th17 compartment.