The study of mucosal fungal commensal communities and infection in SIV/HIV

The hallmark of human immunodeficiency virus (HIV) pathogenesis is the progressive depletion of CD4+ T-cell populations including the associated subset Th17.

Dysregulated Th17 response were thought to create the opportunity to the fungal commensal Candida albicans to cause mucosal disease.

However, patients with idiopathic CD4+ lymphocytopenia as well as patients with inherited CD4 deficiency both lacking CD4 T cells and Th17 cell-derived IL-17 production are not at risk of developing mucosal candidiasis.

These clinical observations indicate that beyond decreased Th17 cells, accompanying defective production of IL-17-related cytokines by non-Th17 cellular mucosal sources and/or alternative IL-17-independent mechanisms must contribute to mucosal fungal susceptibility in HIV.

Moreover, how fungal presence and dysbiosis correlate with HIV susceptibility, transmission and progression is unclear.This proposal aims to understand how mucosal tissue viral-fungal dynamics affects host immunity by examining IL-17 dependent and independent antifungal mechanisms at the oral mucosa in simian immunodeficiency virus (SIV)-infected non-Human primates or HIV-infected humans.

Additionally, we aim to understand the role of vaginal mycobiota for SIV transmission and progression.Knowledge of the mechanisms of mucosal immunity during HIV/SIV and the relationship between HIV and C. albicans will enhance our understanding of mucosal immune mechanisms and create new therapeutic approaches