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TY - JOUR AU - Mattner, Jochen AU - DeBord, Kristin L. AU - Ismail, Nahed AU - Goff, Randal D. AU - Cantu, Carlos AU - Zhou, Dapeng AU - Saint-Mezard, Pierre AU - Wang, Vivien AU - Gao, Ying AU - Yin, Ning AU - Hoebe, Kasper AU - Schneewind, Olaf AU - Walker, David AU - Beutler, Bruce AU - Teyton, Luc AU - Savage, Paul B. AU - Bendelac, Albert PY - 2005 DA - 2005/03/01 TI - Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections JO - Nature SP - 525 EP - 529 VL - 434 IS - 7032 AB - 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. SN - 1476-4687 UR - https://doi.org/10.1038/nature03408 DO - 10.1038/nature03408 ID - Mattner2005 ER -