Journal
CELL
Volume 156, Issue 1-2, Pages 123-133Publisher
CELL PRESS
DOI: 10.1016/j.cell.2013.11.042
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Funding
- NIH [AI090102, DK44319, DK51362, DK53056, DK88199, AI007061]
- Crohn's and Colitis Foundation of America Senior Research Award
- Crohn's and Colitis Foundation of America Postdoctoral Fellowship Award
- Deutsche Forschungsgemeinschaft (DFG) [OL 324/1-1]
- DFG [ZE814/4-1]
- ERC [336528]
- Harvard Digestive Diseases Center [DK034854]
- European Research Council (ERC) [336528] Funding Source: European Research Council (ERC)
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Coevolution of beneficial microorganisms with the mammalian intestine fundamentally shapes mammalian physiology. Here, we report that the intestinal microbe Bacteroides fragilis modifies the homeostasis of host invariant natural killer T (iNKT) cells by supplementing the host's endogenous lipid antigen milieu with unique inhibitory sphingolipids. The process occurs early in life and effectively impedes iNKT cell proliferation during neonatal development. Consequently, total colonic iNKT cell numbers are restricted into adulthood, and hosts are protected against experimental iNKT cell-mediated, oxazolone- induced colitis. In studies with neonatal mice lacking access to bacterial sphingolipids, we found that treatment with B. fragilis glycosphingolipids-exemplified by an isolated peak (MW = 717.6) called GSL-Bf717-reduces colonic iNKT cell numbers and confers protection against oxazolone-induced colitis in adulthood. Our results suggest that the distinctive inhibitory capacity of GSL-Bf717 and similar molecules may prove useful in the treatment of autoimmune and allergic disorders in which iNKT cell activation is destructive.
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