2. Academic Validation
  3. CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi

CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi

  • Science. 2018 Jan 12;359(6372):232-236. doi: 10.1126/science.aao1503.
Irina Leonardi 1 2,  Xin Li 1 2,  Alexa Semon 1 2,  Dalin Li 3,  Itai Doron 1 2,  Gregory Putzel 2,  Agnieszka Bar 1 2,  Daniel Prieto 4,  Maria Rescigno 5,  Dermot P B McGovern 3,  Jesus Pla 4,  Iliyan D Iliev 1 2 6
Affiliations

Affiliations

  • 1 Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA.
  • 2 The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10021, USA.
  • 3 The F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • 4 Faculty of Pharmacy, Department of Microbiology II, Universidad Complutense de Madrid, 28040 Madrid, Spain.
  • 5 Department of Experimental Oncology, European Institute of Oncology, I-20141 Milan, Italy.
  • 6 Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY 10065, USA.
PMID: 29326275 DOI: 10.1126/science.aao1503
Abstract

Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential in modulating host immune homeostasis and inflammatory disease. Nonetheless, the mechanisms governing immunity to gut Fungal communities (mycobiota) remain unknown. We identified CX3CR1+ mononuclear phagocytes (MNPs) as being essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+ MNPs express Antifungal receptors and activate Antifungal responses in a Syk-dependent manner. Genetic ablation of CX3CR1+ MNPs in mice led to changes in gut Fungal communities and to severe colitis that was rescued by Antifungal treatment. In Crohn's disease patients, a missense mutation in the gene encoding CX3CR1 was identified and found to be associated with impaired Antifungal responses. These results unravel a role of CX3CR1+ MNPs in mediating interactions between intestinal mycobiota and host immunity at steady state and during inflammatory disease.

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