Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis

By I. Iliev, Vincent A. Funari, K. Taylor, Quoclinh Nguyen, C. Reyes, Samuel P. Strom, Jordan Brown, Courtney A. Becker, P. Fleshner, M. Dubinsky and 5 more. Science, 2012

999 citations recorded by the source corpus.

The Mycobiome In the past few years, much attention has been given to the trillions of bacterial inhabitants in our guts and the myriad of ways in which they influence our overall health. But what about fungi? Iliev et al. (p. 1314) now report that mice and humans, along with several other mammals, contain a resident intestinal population of fungi. Deletion of Dectin-1, which acts as a major innate immune sensor for fungi, led to enhanced susceptibility and worse pathology in a chemically induced model of colitis in mice. A polymorphism in the gene that encodes Dectin-1 has been observed in patients with ulcerative colitis, which hints that, besides the traditional bacterial microbiome, alterations in the “mycobiome” may also play a role in health and disease. Mammals contain resident fungal intestinal populations that influence disease susceptibility. 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.

Subfields: Immunology, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/171ea786ca13fda0861556a017c1c8a6099ff067

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Citations in the corpus

Archaea and Fungi of the Human Gut Microbiome: Correlations with Diet and Bacterial Residents (2013, background): “Recent work using a murine model has suggested that normally mutualistic or commensal fungi species may exacerbate intestinal inflammation in mice with sensitized genotypes [33].”
Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn’s Disease (2015, background): “, 1998), and fungi have shown to exacerbate colitis in mouse models (Iliev et al., 2012).”
Homeostatic immunity and the microbiota (2017, positive): “In the gastrointestinal tract, experimentally, interaction of commensal fungi with the C-type lectin receptor Dectin-1 was able to prevent inflammation in the context of acute mucosal injury (Iliev et al., 2012).”
INTERLEUKIN-4- AND INTERLEUKIN-13-MEDIATED ALTERNATIVELY ACTIVATED MACROPHAGES: ROLES IN HOMEOSTASIS AND DISEASE (2013, positive): “Dectin-1 (Clec7a) is an AAM-associated CLR that is expressed on macrophages, neutrophils, and DCs, among other cells, and is increasingly recognized as the principal PRR in mediating fungal recognition in mice (78, 79) and humans (80).”
Conducting a Microbiome Study (2014, background): “In principle, the bioinformatics pipeline is the same for eukaryoticmarker genes as for bacterial marker genes (Iliev et al., 2012).”
Role of the Microbiota in Immunity and inflammation (2014, background): “In the gastrointestinal tract, experimentally, interaction of commensal fungi with the C type lectin receptor Dectin 1 was able to prevent inflammation in the context of acute mucosal injury (Iliev et al., 2012).”
Hidden Killers: Human Fungal Infections (2012, neutral): “The potential role of fungal pathogens in the immune pathology of inflammatory and autoimmune diseases — for example, Crohn ’ s disease, sarcoidosis, colitis ( 55 ), and arthritis — also requires attention by scientists.”
Defining dysbiosis and its influence on host immunity and disease (2014, background): “A recent study highlighted the importance of controlling fungal overgrowth to intestinal health by investigating the role of Dectin-1 within the gut (Iliev et al., 2012).”
Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. (2013, positive): “Considering the reciprocal influence between the fungal community in the gut and local levels of inflammation (Iliev et al., 2012), IAld might represent a prototypical candidate capable of multitasking effectively in transplanted recipients and patients with mucosal inflammatory diseases.”