HIV Modulates Oral Mucosal Calprotectin and Candidiasis

DESCRIPTION (provided by applicant): Calprotectin is a candidacidal protein complex that is constitutively expressed by squamous mucosal epithelial cells. Epithelial cells expressing calprotectin appear to form a barrier to hyphal penetration. During HIV infection the expression and release of calprotectin into saliva is significantly reduced suggesting that expression of mucosal epithelial calprotectin is impaired. In AIDS, calprotectin is down-regulated and the risk of candidiasis increases. Cross talk between keratinocytes and infected immature dendritic and other immune cells are likely to play a significant role in the translocation of HIV, down regulation of calprotectin and the occurrence of candidiasis. We hypothesize, therefore, that HIV infection of oral mucosal epithelial cells down-regulates calprotectin to reduce resistance to Candida. To test this hypothesis, we will 1) determine the requirement of oral mucosal epithelial calprotectin in transcytosis of HIV; 2) determine if uptake of HIV into oral epithelial cells regulates expression of calprotectin-specific mRNA; 3) ascertain if dendritic or other immune cells cooperate with oral keratinocytes during HIV infection to down-regulate expression of calprotectin; 4) analyze oral epithelial cells before and after transcytosis for susceptibility to Candida infection; and 5) determine if susceptibility to Candida infection is associated with down-regulation of calprotectin. Collectively these experiments will suggest the basis for calprotectin protection against Candida infections, how innate immunity is thwarted in AIDS, and will set the stage to precisely define these mechanisms in a subsequent R01 application.