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

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

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish
Pages (from-to)1767-1778
Number of pages12
JournalCell Reports
Volume23
Issue number6
DOIs
Publication statusPublished - May 8 2018

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Renga, G., Moretti, S., Oikonomou, V., Borghi, M., Zelante, T., Paolicelli, G., Costantini, C., De Zuani, M., Villella, V. R., Raia, V., Del Sordo, R., Bartoli, A., Baldoni, M., Renauld, J. C., Sidoni, A., Garaci, E., Maiuri, L., Pucillo, C., & Romani, L. (2018). IL-9 and Mast Cells Are Key Players of Candida albicans Commensalism and Pathogenesis in the Gut. Cell Reports, 23(6), 1767-1778. https://doi.org/10.1016/j.celrep.2018.04.034