Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis.
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.
Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Iliyan D
ID
Iliev
Vincent A
VA
Funari
Kent D
KD
Taylor
Quoclinh
Q
Nguyen
Christopher N
CN
Reyes
Samuel P
SP
Strom
Jordan
J
Brown
Courtney A
CA
Becker
Phillip R
PR
Fleshner
Marla
M
Dubinsky
Jerome I
JI
Rotter
Hanlin L
HL
Wang
Dermot P B
DP
McGovern
Gordon D
GD
Brown
David M
DM
Underhill
D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D041022:Candida tropicalis / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology*; D003106:Colon / Q000276:immunology / Q000382:microbiology*; D015169:Colony Count, Microbial; D016264:Dextran Sulfate; D004198:Disease Susceptibility; D005260:Female; D005658:Fungi / Q000145:classification / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology*; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D037181:Lectins, C-Type / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D054892:Metagenome; D051379:Mice; D008810:Mice, Inbred C57BL; D020641:Polymorphism, Single Nucleotide; D000099181:Dectin-1
D000908:Antibodies, Fungal; D016264:Dextran Sulfate; D037181:Lectins, C-Type; D000099181:Dectin-1; C546929:CLEC7A protein, human