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Science 336 (6086): 1314-1317

Copyright © 2012 by the American Association for the Advancement of Science

Interactions Between Commensal Fungi and the C-Type Lectin Receptor Dectin-1 Influence Colitis

Iliyan D. Iliev,1 Vincent A. Funari,2,3 Kent D. Taylor,2 Quoclinh Nguyen,2 Christopher N. Reyes,1 Samuel P. Strom,2 Jordan Brown,2 Courtney A. Becker,1 Phillip R. Fleshner,4 Marla Dubinsky,1,5 Jerome I. Rotter,2 Hanlin L. Wang,6 Dermot P. B. McGovern,1,2 Gordon D. Brown,7 David M. Underhill1,6,8,*

Abstract: The intestinal microflora, typically equated with bacteria, influences diseases such as obesity and inflammatory bowel disease. Here, we show that the mammalian gut contains a rich fungal community that interacts with the immune system through the innate immune receptor Dectin-1. Mice lacking Dectin-1 exhibited increased susceptibility to chemically induced colitis, which was the result of altered responses to indigenous fungi. In humans, we identified a polymorphism in the gene for Dectin-1 (CLEC7A) that is strongly linked to a severe form of ulcerative colitis. Together, our findings reveal a eukaryotic fungal community in the gut (the "mycobiome") that coexists with bacteria and substantially expands the repertoire of organisms interacting with the intestinal immune system to influence health and disease.

1 Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
2 Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
3 Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
4 Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
5 Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
6 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
7 Section of Immunology and Infection, Division of Applied Medicine, Institute of Medical Sciences and The Aberdeen Fungal Group, University of Aberdeen, Aberdeen AB24 2ZD, UK.
8 Research Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

* To whom correspondence should be addressed. E-mail: david.underhill{at}csmc.edu

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