As of November 2007, there were 33.2 million people living with HIV/AIDS worldwide. Of these individuals, as many as 90 percent have had or are currently suffering from oropharyngeal candidiasis, the most common oral manifestation of HIV/AIDS. Oropharyngeal candidiasis is an overgrowth of the commensal yeast
Candida albicans, which can result in potentially serious infections of the mouth, pharynx, gastrointestinal tract, with often fatal dissemination in the blood. Previously we found that expression of pro-inflammatory cytokines and chemokines, IL-1α, IL-1β, IL-6, IL-8, and other innate immune molecules, SLPI, hBD-2, S100A8, S100A9, and TLR2 were down-regulated 2- to 3-fold in HIV-1 infected keratinocyte cultures. Objective: We hypothesized that HIV-1 makes oral keratinocytes more susceptible to penetration of Candida through the plasma membrane. Methods: To determine whether HIV-1 decreases epithelial resistance to Candida, monolayers of immortalized oral keratinocytes (TERT-2 cells) were infected with HIV-1 (BaL or IIIb) and incubated for 24 hrs. Post HIV infection, the monolayers were co-infected with
C. albicans and incubated for an additional 2 hrs. Double immunofluorescence staining was used to identify Candida pseudohyphae penetrating TERT-2 cells. The percentage of TERT-2 cells invaded by Candida, and the percentage of Candida cells that had invaded each TERT-2 cell were then calculated. Results: Both the percentage of TERT-2 cells invaded by Candida and the percentage of Candida cells that had penetrated a TERT cell were significantly increased by co-infection with HIV-1. Conclusion: These data support the hypothesis that HIV-1 infection decreases the resistance of oral keratinocytes to invasion by
C. albicans.
Supported by NIH R21DE15056, NIH R01DE015503 and the UMSOD Summer Fellowship program.