Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections |
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Authors: | Mattner Jochen Debord Kristin L Ismail Nahed Goff Randal D Cantu Carlos Zhou Dapeng Saint-Mezard Pierre Wang Vivien Gao Ying Yin Ning Hoebe Kasper Schneewind Olaf Walker David Beutler Bruce Teyton Luc Savage Paul B Bendelac Albert |
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Institution: | Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA. |
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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. |
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