Response to Fungal Dysbiosis by Gut-Resident CX3CR1+ Mononuclear Phagocytes Aggravates Allergic Airway Disease

Xin Li; Irina Leonardi; Alexa Semon; Itai Doron; Iris H Gao; Gregory Garbès Putzel; Youngjun Kim; Hiroki Kabata; David Artis; William D Fiers; Amanda E Ramer-Tait; Iliyan D Iliev

doi:10.1016/j.chom.2018.11.003

Response to Fungal Dysbiosis by Gut-Resident CX3CR1⁺ Mononuclear Phagocytes Aggravates Allergic Airway Disease

Cell Host Microbe. 2018 Dec 12;24(6):847-856.e4. doi: 10.1016/j.chom.2018.11.003. Epub 2018 Nov 29.

Authors

Affiliations

¹ Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
² Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
³ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
⁴ Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
⁵ Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
⁶ Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA.
⁷ Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA. Electronic address: iliev@med.cornell.edu.

Abstract

Sensing of the gut microbiota, including fungi, regulates mucosal immunity. Whether fungal sensing in the gut can influence immunity at other body sites is unknown. Here we show that fluconazole-induced gut fungal dysbiosis has persistent effects on allergic airway disease in a house dust mite challenge model. Mice with a defined community of bacteria, but lacking intestinal fungi were not susceptible to fluconazole-induced dysbiosis, while colonization with a fungal mixture recapitulated the detrimental effects. Gut-resident mononuclear phagocytes (MNPs) expressing the fractalkine receptor CX3CR1 were essential for the effect of gut fungal dysbiosis on peripheral immunity. Depletion of CX3CR1⁺ MNPs or selective inhibition of Syk signaling downstream of fungal sensing in these cells ameliorated lung allergy. These results indicate that disruption of intestinal fungal communities can have persistent effects on peripheral immunity and aggravate disease severity through fungal sensing by gut-resident CX3CR1⁺ MNPs.

Keywords: CX3CR1(+) mononuclear phagocytes; fungi; gut-lung axis; mycobiome; mycobiota dysbiosis.

Publication types

Comment

MeSH terms

Animals
CX3C Chemokine Receptor 1
Dysbiosis*
Fungi
Hypersensitivity*
Intestines
Mice
Phagocytes

Substances

CX3C Chemokine Receptor 1
Cx3cr1 protein, mouse

Abstract

Publication types

MeSH terms

Substances

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