Candida-Host Interactions in HIV Disease

Oropharyngeal candidiasis (OPC), caused by Candida albicans, is the most common oral infection in HIV+ persons. Although Th1-type CD4+ T cells are the predominant host defense mechanism against OPC, CD8+ T cells and epithelial cells become important when blood CD4+ T cells are reduced below a protective threshold during progression to AIDS. In an early cross-sectional study, OPC+ tissue biopsied from HIV+ persons had an accumulation of activated memory CD8+ T cells at the epithelial-lamina propria interface together with reduced expression of the adhesion molecule, E-cadherin; suggesting a protective role for CD8+ T cells, but a dysfunction in the mucosal migration of the cells in those with OPC. In a subsequent one-year longitudinal study, OPC- patients with low oral fungal colonization revealed an unremarkable presence of CD8+ T cells and normal E-cadherin expression. In OPC- patients with high oral Candida colonization (indicative of a pre-clinical OPC condition), higher numbers of CD8+ T cells were observed throughout the tissue with normal E-cadherin expression. In OPC+ patients, where lack of CD8+ T cell migration was associated with reduced E-cadherin, subsequent evaluations following successful treatment of infection revealed normal E-cadherin expression and cellular distribution. Regarding epithelial cell responses, intact oral epithelial cells exhibit fungistatic activity via an acid-labile protein moiety. A proteomic approach revealed that Annexin-A1 is a strong candidate for the effector moiety. Taken together, we hypothesize that under reduced CD4+ T cells, HIV+ persons protected from OPC have CD8+ T cells that migrate to the site of a pre-clinical infection under normal expression of E-cadherin, whereas those with OPC have reduced E-cadherin that is not permanent, but which prohibits CD8+ T cells from migrating for effector function. Concomitantly, oral epithelial cells function through Annexin-A1 to keep Candida in a commensal state, but can be overwhelmed easily contributing to susceptibility to OPC.