Candida albicans Derived Metabolites Modulate HIV Pathogenesis

Objectives: Although HIV-RNA can be detected in saliva, the oral cavity is non-conducive for HIV transmission. The participation of microorganisms in the resistance of oral mucosa remains unknown. Characterizing the responsible factors and their mechanisms of action may identify new opportunities for interference with viral acquisition at mucosal sites. We hypothesized that Candida albicans-metabolites impact HIV pathogenesis.
Methods: Fungal-derived conditioned medium (FM) was prepared from C. albicans (SC5314, 90028, 321182 and 274) in YNB medium. The biological activity of FM on HIV-1 was determined by cell-based assay (TZM-bl, PBMCs) against HIV-1 BaL/R5 or NL43/X4. To elucidate the mechanisms of action, the FM-induced co-cultures (host cell and HIV-1) were harvested for host inflammatory cytokines/chemokines (MIP-1α, MIP-1β, RANTES, IL-8, SDF-1) and host genome expression profiling. The chemical composition of FM was examined via metabolomics and chromatographic/spectroscopic methods.
Results: Co-culture with FM did not affect the cell-viability. All FM strains tested decreased the percentage of HIV infection in comparison to the controls (p<0.01). The mean was 70.47%, 49.46%, 64.31% and 70.55% of inhibition in FM 90028, 274, SC5314, and 321182, respectively. There was no effect on HIV-NL43/X4. FM enhanced the production of CC-chemokine ligands (ccl4, ccl5), modulated the expression of interferons (ifnb1, ifna1, ifng, irf1, irf2), and upregulated the expression of host-restriction factors (apobec3f, apobec3g). Heat treatment and digestion with proteinase-K did not alter the biological properties of Candida-metabolites. The extracellular-microbial factors appeared to be non-proteinaceous molecules that were small and diffusible. HPLC-MS/MS analyses confirmed the composition of the antiviral factor as a glycoprotein-glycan.
Conclusions: The data provide insights on how Candida-metabolites block HIV infection by inducing/upregulating expression of CC-chemokine ligands, interferons, and host-restriction factors. In contrast to the commensalism/parasitism relationship, C. albicans could be involved in oral resistance by reducing the pathogenesis of HIV-1.