Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections

Jochen Mattner, Kristin L. DeBord, Nahed Ismail, Randal D. Goff, Carlos Cantu, Dapeng Zhou, Pierre Saint-Mezard, Vivien Wang, Ying Gao, Ning Yin, Kasper Hoebe, Olaf Schneewind, David Walker, Bruce Beutler, Luc Teyton, Paul B. Savage, Albert Bendelac

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884 Scopus citations

Abstract

CD1d-restricted natural killer T (NKT) cells are innate-like lymphocytes that express a conserved T-cell receptor and contribute to host defence against various microbial pathogens. However, their target lipid antigens have remained elusive. Here we report evidence for microbial, antigen-specific activation of NKT cells against Gram-negative, lipopolysaccharide (LPS)-negative alpha-Proteobacteria such as Ehrlichia muris and Sphingomonas capsulata. We have identified glycosylceramides from the cell wall of Sphingomonas that serve as direct targets for mouse and human NKT cells, controlling both septic shock reaction and bacterial clearance in infected mice. In contrast, Gram-negative, LPS-positive Salmonella typhimurium activates NKT cells through the recognition of an endogenous lysosomal glycosphingolipid, iGb3, presented by LPS-activated dendritic cells. These findings identify two novel antigenic targets of NKT cells in antimicrobial defence, and show that glycosylceramides are an alternative to LPS for innate recognition of the Gram-negative, LPS-negative bacterial cell wall.

Original languageEnglish (US)
Pages (from-to)525-529
Number of pages5
JournalNature
Volume434
Issue number7032
DOIs
StatePublished - Mar 24 2005

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    Mattner, J., DeBord, K. L., Ismail, N., Goff, R. D., Cantu, C., Zhou, D., Saint-Mezard, P., Wang, V., Gao, Y., Yin, N., Hoebe, K., Schneewind, O., Walker, D., Beutler, B., Teyton, L., Savage, P. B., & Bendelac, A. (2005). Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature, 434(7032), 525-529. https://doi.org/10.1038/nature03408