Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells.

Abstract

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.

• Authors: Dingding An, Sungwhan F Oh, Torsten Olszak, Joana F Neves, Fikri Y Avci, Deniz Erturk-Hasdemir, Xi Lu, Sebastian Zeissig, Richard S Blumberg, Dennis L Kasper
• Journal: Cell (Cell) Vol. 156 Issue 1-2 Pg. 123-33 (Jan 16 2014) ISSN: 1097-4172 [Electronic] United States
• PMID: 24439373 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Glycosphingolipids
• Oxazolone

Topics

• Animals
• Animals, Newborn
• Bacteroides fragilis (metabolism)
• Cell Proliferation
• Colitis (chemically induced, immunology, prevention & control)
• Colon (growth & development, microbiology)
• Glycosphingolipids (metabolism)
• Mice
• Mice, Inbred C57BL
• Natural Killer T-Cells (cytology, immunology)
• Oxazolone