Defective IL-17- and IL-22-dependent mucosal host response to determines susceptibility to oral candidiasis in mice expressing the HIV-1 transgene

Abstract

The tissue-signaling cytokines IL-17 and IL-22 are critical to host defense against oral infection, by their induction of oral antimicrobial peptide expression and recruitment of neutrophils. Mucosal Th17 cells which produce these cytokines are preferentially depleted in HIV-infected patients. Here, we tested the hypothesis that defective IL-17- and IL-22-dependent host responses to determine the phenotype of susceptibility to oropharyngeal candidiasis (OPC) in transgenic (Tg) mice expressing HIV-1. Results: Naïve CD4+ T-cells and the differentiated Th1, Th2, Th17, Th1Th17 and Treg lineages were all profoundly depleted in cervical lymph nodes (CLNs) of these Tg mice. However, naive CD4+ cells from Tg mice maintained the capacity to differentiate into these lineages in response to polarizing cytokines. Expression of , and was enhanced in oral mucosal tissue of non-Tg, but not of Tg mice, after oral infection with. Treatment of infected Tg mice with the combination of IL-17 and IL-22, but not IL-17 or Il-22 alone, significantly reduced oral burdens of and abundance of hyphae in the epithelium of tongues of infected Tg mice, and restored the ability of the Tg mice to up-regulate expression of and in response to infection. Conclusions: These findings demonstrate that defective IL-17- and IL-22-dependent induction of innate mucosal immunity to is central to the phenotype of susceptibility to OPC in these HIV transgenic mice.