title: Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections.
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.
authors.affiliation: Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Jochen
authors.initials: J
authors.lastname: Mattner
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Debord
authors.forename: Nahed
authors.initials: N
authors.lastname: Ismail
authors.forename: Randal D
authors.initials: RD
authors.lastname: Goff
authors.forename: Carlos
authors.initials: C
authors.lastname: Cantu
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhou
authors.forename: Pierre
authors.initials: P
authors.lastname: Saint-Mezard
authors.forename: Vivien
authors.initials: V
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Ning
authors.initials: N
authors.lastname: Yin
authors.forename: Kasper
authors.initials: K
authors.lastname: Hoebe
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
authors.forename: David
authors.initials: D
authors.lastname: Walker
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
authors.forename: Luc
authors.initials: L
authors.lastname: Teyton
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology; D055610:Antigens, CD1d; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured; D002518:Ceramides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004536:Ehrlichia / Q000276:immunology / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D012486:Salmonella typhimurium / Q000276:immunology; D012772:Shock, Septic / Q000276:immunology / Q000382:microbiology; D020578:Sphingomonas / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D002518:Ceramides; D008070:Lipopolysaccharides