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 () and
Albert Bendelac ()
Additional contact information
Jochen Mattner: University of Chicago
Kristin L. DeBord: University of Chicago
Nahed Ismail: University of Texas Medical Branch
Randal D. Goff: Brigham Young University
Carlos Cantu: The Scripps Research Institute
Dapeng Zhou: University of Chicago
Pierre Saint-Mezard: University of Chicago
Vivien Wang: University of Chicago
Ying Gao: Brigham Young University
Ning Yin: Brigham Young University
Kasper Hoebe: The Scripps Research Institute
Olaf Schneewind: University of Chicago
David Walker: University of Texas Medical Branch
Bruce Beutler: The Scripps Research Institute
Luc Teyton: The Scripps Research Institute
Paul B. Savage: Brigham Young University
Albert Bendelac: University of Chicago
Nature, 2005, vol. 434, issue 7032, 525-529
Abstract:
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 pathogens1,2. 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.
Date: 2005
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Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:434:y:2005:i:7032:d:10.1038_nature03408
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DOI: 10.1038/nature03408
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