2. Academic Validation
  3. IL-9 and Mast Cells Are Key Players of Candida albicans Commensalism and Pathogenesis in the Gut

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

  • Cell Rep. 2018 May 8;23(6):1767-1778. doi: 10.1016/j.celrep.2018.04.034.
Giorgia Renga 1,  Silvia Moretti 1,  Vasilis Oikonomou 1,  Monica Borghi 1,  Teresa Zelante 1,  Giuseppe Paolicelli 1,  Claudio Costantini 1,  Marco De Zuani 2,  Valeria Rachela Villella 3,  Valeria Raia 4,  Rachele Del Sordo 1,  Andrea Bartoli 1,  Monia Baldoni 5,  Jean-Christophe Renauld 6,  Angelo Sidoni 1,  Enrico Garaci 7,  Luigi Maiuri 8,  Carlo Pucillo 2,  Luigina Romani 9
Affiliations

Affiliations

  • 1 Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy.
  • 2 Department of Medical and Biological Science, University of Udine, 33100 Udine, Italy.
  • 3 European Institute for Research in Cystic Fibrosis, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy.
  • 4 Regional Cystic Fibrosis Center, Pediatric Unit, Department of Translational Medical Sciences, Federico II University Naples, 80131 Naples, Italy.
  • 5 Department of Medicine, University of Perugia, 06132 Perugia, Italy.
  • 6 Ludwig Institute for Cancer Research, Brussels Branch, 1200 Brussels, Belgium.
  • 7 San Raffaele Pisana, IRCCS, Telematic University and University of Tor Vergata, 00163 Rome, Italy.
  • 8 European Institute for Research in Cystic Fibrosis, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy; Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy.
  • 9 Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy. Electronic address: [email protected].
PMID: 29742432 DOI: 10.1016/j.celrep.2018.04.034
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.

Keywords

Candida albicans; IDO1; IL-9; celiac disease; intestinal inflammation; mast cells.

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