IL-9 and Mast Cells Are Key Players of Candida Albicans Commensalism and Pathogenesis in the Gut

Abstract

Candida albicans is implicated in intestinal diseases. Identifying host signatures that discriminate between the pathogenic vs commensal nature of this human commensal is clinically relevant. In the present study we have identified IL-9 and mast cells (MC) as key players of Candida commensalism and pathogenicity. By inducing TGF-β in stromal MC, IL-9 pivotally contributed to mucosal immune tolerance via the indoleamine 2,3-dioxygenase enzyme. However, Candida-driven IL-9 and mucosal MC also contributed to barrier function loss, dissemination and inflammation in experimental leaky gut models and were upregulated in patients with celiac disease. Inflammatory dysbiosis occurred in IL-9 and MC deficiency, a finding indicating that the activity of IL-9 and MC may go beyond host immunity to include regulation of the microbiota. Thus, the output of the IL9/MC axis is highly contextual during Candida colonization and reveals how host immunity and the microbiota finely tune Candida behavior in the gut.