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CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi

Irina Leonardi1,2, Xin Li1,2, Alexa Semon1,2

  • 1Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA.

Science (New York, N.Y.)
|January 13, 2018
PubMed

Insights

CX3CR1+ mononuclear phagocytes (MNPs) are crucial for initiating immune responses against intestinal fungi. Their absence causes gut dysbiosis and colitis, highlighting their role in maintaining gut health and immunity.

Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • Intestinal fungi (mycobiota) influence host immune homeostasis and inflammatory diseases.
  • Mechanisms of immunity against gut fungal communities are largely unknown.

Purpose of the Study:

  • To identify key immune cells and mechanisms involved in host immunity to intestinal fungi.
  • To investigate the role of CX3CR1+ mononuclear phagocytes (MNPs) in gut fungal immunity and inflammatory conditions.

Main Methods:

  • Identification of CX3CR1+ MNPs as essential for antifungal immune responses.
  • Analysis of Syk-dependent activation of antifungal responses by MNPs.
  • Genetic ablation of CX3CR1+ MNPs in mice to study effects on mycobiota and colitis.
  • Investigation of CX3CR1 mutations in Crohn's disease patients.

Main Results:

  • CX3CR1+ MNPs express antifungal receptors and mediate Syk-dependent antifungal responses.
  • Mice lacking CX3CR1+ MNPs exhibited altered gut fungal communities and severe colitis.
  • Antifungal treatment rescued colitis in mice lacking CX3CR1+ MNPs.
  • A CX3CR1 gene mutation associated with impaired antifungal responses was found in Crohn's disease patients.

Conclusions:

  • CX3CR1+ MNPs are essential for initiating innate and adaptive immune responses to intestinal fungi.
  • These cells play a critical role in host-mycobiota interactions at steady state and during inflammation.
  • Dysfunction in CX3CR1+ MNPs may contribute to inflammatory bowel diseases like Crohn's disease.

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