Activation of Th1 and Th17-polarised responses in experimental oral candidiasis

Oral candidiasis is caused by the commensal Candida albicans, and affects immunocompromised individuals. Clinical observations and experimental data from our laboratory suggest that CD4+ T-cells, and the p40 subunit of interleukins-12 and 23 are strict prerequisites for resistance against oral candidiasis. Objectives: To elucidate the exact involvement of IL-12 and IL-23 in protection against oral candidiasis in a mouse model. Methods: IL-12/23p40 knockout (KO) mice and C57BL/6 wild-type controls (WT) were infected orally with 1×10⁸ C. albicans yeasts, then oral tissues and draining lymph nodes were isolated at various timepoints after infection. Affymetrix cDNA microarray analysis and quantitative RT-PCR was undertaken with particular interest in the putative roles of IL-12, IL-23, IL-17 and T helper (Th)17 cells. Results: Microarray analysis showed that genes involved in antigen presentation and T-cell differentiation were down-regulated in KO mice, perhaps due to an imbalance of immunosuppressive cytokines in a p40-deficient environment. There was an increase in the expression of p19, p35 and p40 mRNAs one day after infection in the lymph nodes of WT mice, but no significant changes in IL-17 levels in either KO or WT. There was however an increase in IL-17 expression in the oral tissues of WT mice post-infection, while TGF-beta was reduced in WT, but up-regulated in KO mice at day 1. Furthermore, there were increases in both p35 and p19 in oral tissues of KO mice in response to infection, perhaps a compensatory effect in the absence of effective mucosal immunity. Conclusion: Data to date suggests that there is no adaptive immune response to oral C. albicans infection in WT mice, but that there appears be local IL-17 production in the oral mucosa, and that IL-17 pathways are not engaged in p40 knockout mice. Funded by the Australian Dental Research Foundation.