Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections

Jochen Mattner; Kristin L Debord; Nahed Ismail; Randal D Goff; Carlos Cantu 3rd; Dapeng Zhou; Pierre Saint-Mezard; Vivien Wang; Ying Gao; Ning Yin; Kasper Hoebe; Olaf Schneewind; David Walker; Bruce Beutler; Luc Teyton; Paul B Savage; Albert Bendelac

doi:10.1038/nature03408

Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections

Nature. 2005 Mar 24;434(7032):525-9. doi: 10.1038/nature03408.

Authors

Jochen Mattner¹, Kristin L Debord, Nahed Ismail, Randal D Goff, Carlos Cantu 3rd, Dapeng Zhou, Pierre Saint-Mezard, Vivien Wang, Ying Gao, Ning Yin, Kasper Hoebe, Olaf Schneewind, David Walker, Bruce Beutler, Luc Teyton, Paul B Savage, Albert Bendelac

Affiliation

¹ Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.

PMID: 15791258
DOI: 10.1038/nature03408

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Antigens, Bacterial / chemistry
Antigens, Bacterial / immunology*
Antigens, Bacterial / pharmacology
Antigens, CD1 / genetics
Antigens, CD1 / immunology
Antigens, CD1d
Cell Wall / chemistry
Cell Wall / immunology
Cells, Cultured
Ceramides / chemical synthesis
Ceramides / chemistry
Ceramides / immunology*
Ceramides / pharmacology
Dendritic Cells / drug effects
Dendritic Cells / immunology
Ehrlichia / immunology
Ehrlichia / isolation & purification
Gram-Negative Bacterial Infections / immunology*
Gram-Negative Bacterial Infections / microbiology
Humans
Killer Cells, Natural / drug effects
Killer Cells, Natural / immunology*
Lipopolysaccharides / pharmacology
Lymphocyte Activation / drug effects
Lymphocyte Activation / immunology*
Mice
Salmonella typhimurium / immunology
Shock, Septic / immunology
Shock, Septic / microbiology
Sphingomonas / immunology
Spleen / immunology
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / immunology*

Substances

Antigens, Bacterial
Antigens, CD1
Antigens, CD1d
CD1D protein, human
Ceramides
Lipopolysaccharides