Editors' ChoiceSYMBIOSIS

Bacterial Lipids Help Gut It Out

Sci. Signal.  28 Jan 2014:
Vol. 7, Issue 310, pp. ec25
DOI: 10.1126/scisignal.2005116

Microbes that populate the gastrointestinal tract influence animal physiology. Thus, understanding the signals that enable the host immune system to select and maintain beneficial species in the gut can inform therapies that promote human health. An et al. found that some bacteria produce lipids that influence the neonatal development of innate immune cells and protect against colitis in adults. Invariant natural killer T cells (iNKTs) recognize lipid antigens presented by the class I major histocompatibility complex–like protein CD1d and are activated by glycosphingolipids produced by pathogenic bacteria. The authors identified a gene in the commensal species Bacteroides fragilis that encoded a protein homologous to serine palmitoyltransferase (SPT), an obligate enzyme in the eukaryotic sphingolipid biosynthetic pathway. Monocolonizing neonatal mice with B. fragilis deleted for the SPT gene (BFΔSPT) promoted proliferation of iNKTs, leading to increased numbers of iNKTs in adults, which were more susceptible to experimentally induced colitis than those colonized with wild-type B. fragilis (BFWT) as neonates. Functional testing of sphingolipid fractions isolated from B. fragilis revealed that a specific α-galactosylceramide (GSL-Bf717) inhibited activation of iNKTs in mice and iNKT hybridomas in culture and reduced the binding of CD1d to iNKTs in the presence of synthetic lipid agonists. Gavage of GSL-Bf717 into mouse pups colonized with BFΔSPT reduced proliferation of iNKTs, leading to fewer iNKTs and reduced susceptibility to experimentally induced colitis in adults. Thus, beneficial bacteria use lipids to signal to the developing host immune system to establish a self-promoting environment that may protect the host from infection by pathogenic species in adulthood.

D. An, S. F. Oh, T. Olszak, J. F. Neves, F. Y. Avci, D. Erturk-Hasdemir, X. Lu, S. Zeissig, R. S. Blumberg, D. L. Kasper, Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells. Cell 156, 123–133 (2014). [PubMed]

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