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 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.

• Authors: Giorgia Renga, Silvia Moretti, Vasilis Oikonomou, Monica Borghi, Teresa Zelante, Giuseppe Paolicelli, Claudio Costantini, Marco De Zuani, Valeria Rachela Villella, Valeria Raia, Rachele Del Sordo, Andrea Bartoli, Monia Baldoni, Jean-Christophe Renauld, Angelo Sidoni, Enrico Garaci, Luigi Maiuri, Carlo Pucillo, Luigina Romani
• Journal: Cell reports (Cell Rep) Vol. 23 Issue 6 Pg. 1767-1778 (05 08 2018) ISSN: 2211-1247 [Electronic] United States
• PMID: 29742432 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• IDO1 protein, mouse
• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Interleukin-9
• Receptors, Interleukin-9

Topics

• Adaptive Immunity
• Animals
• Candida albicans (pathogenicity)
• Candidiasis (immunology, microbiology, pathology)
• Celiac Disease (immunology, pathology)
• Cell Membrane Permeability
• Disease Models, Animal
• Epithelial Cells (microbiology, pathology)
• Humans
• Immunity, Innate
• Indoleamine-Pyrrole 2,3,-Dioxygenase (metabolism)
• Interleukin-9 (metabolism)
• Intestinal Mucosa (immunology, microbiology, pathology)
• Intestines (microbiology, pathology)
• Mast Cells (metabolism)
• Mice, Inbred C57BL
• Receptors, Interleukin-9 (metabolism)
• Signal Transduction
• Up-Regulation