An IL-17-DUOX2 axis controls gastrointestinal colonization by Candida albicans

Candida albicans is a ubiquitous fungus in the human gut yet there is little understanding as to how crosstalk between the fungus and the host regulates gut colonization. Here, we performed global expression profiling on germ-free mice colonized with C. albicans and found that Duox2 and Duoxa2, encoding a dual NADPH oxidase activity, were upregulated in the ileum and colon. Induction of Duox2/Duoxa2 was dependent on both candidalysin toxin secreted by C. albicans hyphae and host IL-17 receptor signaling. IL-17A stimulation of colonoids also efficiently induced Duox2/Duoxa2 expression together with the concomitant production of hydrogen peroxide. The IL-17-DUOX2 axis significantly impacted C. albicans gut commensalism; loss of IL-17 signaling increased colonization whereas loss of DUOX2 activity reduced colonization. These results reveal how a complex interplay between C. albicans toxin production and a host IL-17-DUOX2 axis regulates fungal gut colonization.