Oral epithelial IL-22/STAT3 signaling licenses IL-17–mediated immunity to oral mucosal candidiasis.

Autor: Aggor, Felix E. Y., Break, Timothy J., Trevejo-Nuñez, Giraldina, Whibley, Natasha, Coleman, Bianca M., Bailey, Rachel D., Kaplan, Daniel H., Naglik, Julian R., Shan, Wei, Shetty, Amol C., McCracken, Carrie, Durum, Scott K., Biswas, Partha S., Bruno, Vincent M., Kolls, Jay K., Lionakis, Michail S., Gaffen, Sarah L.
Zdroj: Science Immunology; 2020, Vol. 5 Issue 48, p1-15, 15p
Abstrakt: Type 17 tag team: Effective immune defense against invasive oral infections by the fungus Candida albicans relies heavily on the cytokine IL-17A and its ability to stimulate a coordinated antifungal response by the multilayered oral epithelium. Aggor et al. used a mouse model of oral candidiasis to investigate the contribution of IL-22, another cytokine produced by many type 17 lymphocytes, to antifungal immunity. The rapid induction of IL-22 after oral Candida infection enhanced IL-22–dependent proliferation of the basal epithelial layer, thereby sustaining the ability of suprabasal epithelial cells expressing IL-17 receptors to respond to IL-17A with induction of immune effectors capable of repelling fungal infection. These findings provide new mechanistic insights into the cooperative antifungal effects of IL-22 and IL-17A in defending the host against oral candidiasis. Oropharyngeal candidiasis (OPC; thrush) is an opportunistic infection caused by the commensal fungus Candida albicans. Interleukin-17 (IL-17) and IL-22 are cytokines produced by type 17 lymphocytes. Both cytokines mediate antifungal immunity yet activate quite distinct downstream signaling pathways. While much is now understood about how IL-17 promotes immunity in OPC, the activities of IL-22 are far less well delineated. We show that, despite having similar requirements for induction from type 17 cells, IL-22 and IL-17 function nonredundantly during OPC. We find that the IL-22 and IL-17 receptors are required in anatomically distinct locations within the oral mucosa; loss of IL-22RA1 or signal transducer and activator of transcription 3 (STAT3) in the oral basal epithelial layer (BEL) causes susceptibility to OPC, whereas IL-17RA is needed in the suprabasal epithelial layer (SEL). Transcriptional profiling of the tongue linked IL-22/STAT3 not only to oral epithelial cell proliferation and survival but also, unexpectedly, to driving an IL-17–specific gene signature. We show that IL-22 mediates regenerative signals on the BEL that replenish the IL-17RA–expressing SEL, thereby restoring the ability of the oral epithelium to respond to IL-17 and thus to mediate antifungal events. Consequently, IL-22 signaling in BEL "licenses" IL-17 signaling in the oral mucosa, revealing spatially distinct yet cooperative activities of IL-22 and IL-17 in oral candidiasis. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index