Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections.
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.
Mattner
Jochen
J
Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.
Debord
Kristin L
KL
Ismail
Nahed
N
Goff
Randal D
RD
Cantu
Carlos
C
Zhou
Dapeng
D
Saint-Mezard
Pierre
P
Wang
Vivien
V
Gao
Ying
Y
Yin
Ning
N
Hoebe
Kasper
K
Schneewind
Olaf
O
Walker
David
D
Beutler
Bruce
B
Teyton
Luc
L
Savage
Paul B
PB
Bendelac
Albert
A
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*
D000942:Antigens, Bacterial; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D002518:Ceramides; D008070:Lipopolysaccharides