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

• Published in: Cell reports (Cambridge) Vol. 23; no. 6; pp. 1767 - 1778
• Main Authors: Renga, Giorgia, Moretti, Silvia, Oikonomou, Vasilis, Borghi, Monica, Zelante, Teresa, Paolicelli, Giuseppe, Costantini, Claudio, De Zuani, Marco, Villella, Valeria Rachela, Raia, Valeria, Del Sordo, Rachele, Bartoli, Andrea, Baldoni, Monia, Renauld, Jean-Christophe, Sidoni, Angelo, Garaci, Enrico, Maiuri, Luigi, Pucillo, Carlo, Romani, Luigina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.05.2018; Cell Press; Elsevier
• Subjects: Adaptive Immunity; Animals; Candida albicans; Candida albicans - pathogenicity; Candidiasis - immunology; Candidiasis - microbiology; Candidiasis - pathology; celiac disease; Celiac Disease - immunology; Celiac Disease - pathology; Cell Membrane Permeability; Disease Models, Animal; Epithelial Cells - microbiology; Epithelial Cells - pathology; Humans; IDO1; IL-9; Immunity, Innate; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Interleukin-9 - metabolism; intestinal inflammation; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Intestines - microbiology; Intestines - pathology; mast cells; Mast Cells - metabolism; Mice, Inbred C57BL; Receptors, Interleukin-9 - metabolism; Signal Transduction; Up-Regulation; Candida albicans; celiac disease; intestinal inflammation; mast cells; IL-9; IDO1
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.04.034

Candida albicans is implicated in intestinal diseases. Identifying host signatures that discriminate between the pathogenic versus commensal nature of this human commensal is clinically relevant. In the present study, we identify IL-9 and mast cells (MCs) as key players of Candida commensalism and pathogenicity. By inducing TGF-β in stromal MCs, IL-9 pivotally contributes to mucosal immune tolerance via the indoleamine 2,3-dioxygenase enzyme. However, Candida-driven IL-9 and mucosal MCs also contribute to barrier function loss, dissemination, and inflammation in experimental leaky gut models and are upregulated in patients with celiac disease. Inflammatory dysbiosis occurs with IL-9 and MC deficiency, indicating that the activity of IL-9 and MCs may go beyond host immunity to include regulation of the microbiota. Thus, the output of the IL-9/MC axis is highly contextual during Candida colonization and reveals how host immunity and the microbiota finely tune Candida behavior in the gut. [Display omitted] •IL-9/IL-9R signaling affects MC function in mucosal candidiasis•IL-9 and mucosal MCs contribute to barrier function loss in leaky gut models•IL-9 and stromal MCs induce local protective tolerance in infection via IDO1•IL-9 and mucosal MCs expand and IDO1 decreases in human celiac disease Deciphering the mechanisms by which Candida albicans promotes either pathology or protective tolerance in the gut could be clinically relevant. Renga et al. show a key role for IL-9 and mast cells in promoting either inflammatory dysbiosis and pathology or tolerance in leaky gut models and human celiac disease.