Characterization of Epithelial Responses to Candida Albicans and HIV-1 Infection

Objectives: Candida carriage rates amongst HIV-negative persons is approximately 50%. Candida albicans, is the most common oral infection in HIV disease, 90% of HIV-infected individuals will develop oral candidiasis during their progression to full-blown AIDS. Such a high level of co-infection implies that HIV induces a profound perturbation of the oral mucosa resulting in specific alterations that promote co-infection. In an attempt to assess how epithelial cell responses to a common commensal organism might affect HIV infection, we studied the impact of Candida infection on oral (TR146) and vaginal (A431) epithelial cell lines. We have also investigated the impact of HIV infection on the epithelium to determine if this direct interaction may in part be responsible for the altered virulence of C. albicans in HIV-positive subjects

Methods: Gene expression levels were measured by real-time qRT-PCR. Western blot analysis using antibodies to HIV gp160 was used to detect virus binding to Candida.

Results: Preliminary studies indicate that C. albicans infection of epithelial cells results in the upregulation of the HIV co-receptor CCR5, the non-canonical receptors syndecan 1 and 4 and ICAM-1, IRF-1, a transcription factor associated with HIV infection was also upregulated. Early studies also indicate that HIV directly binds to several Candida species.

Conclusions: Our data shows that infection with C. albicans appears to alter expression of specific genes that may promote HIV infection. However we are yet to determine if binding is X4 or R5 co-receptor specific, whether or not it is modulated by Candida growth in the yeast or the hyphal phase and the potential fate of captured / bound HIV, i.e. does Candida remain infectious?