Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections

Mattner, J. et al. Nature 434, 525-529, 2005

Speaker: 葉恭誌                        Date: 2005/12/07 15:00-16:00

Commentator: 凌斌老師                  Place: 601教室

Abstract:

     Nature killer T (NKT) cells are innate-like lymphocytes. They express an invariant and conserved T-cell receptor (composed of Va14-Ja18 in mice and the homologous Va24-Ja18 in humans) that recognizes glycolipid antigens presented by CD1d (1). NKT cells are activated during various bacteria infections, but the target lipid antigens activating these cells have remained elusive. The authors used one LPS-positive Gram-negative bacterium- Salmonella typhimurium and two LPS-negative Gram-negative bacteria- Sphingomonas capsulata and Ehrichia muris for experiments. Co-culture these bacteria with dendritic cells and NKT cells all induced the production of IFN-g. When blocked the TLR signalling or endogenous glycolipid ligand isoglobotrihexosylceramide (iGb3), the response to Salmonella typhimurium was prevented, suggesting that the TLR signalling and endogenous glygolipid- iGb3 was essential for Salmonella typhimurium to activate NKT cells. Presentation of synthetic glycosylceramides from Sphingomonas spp. by CD1d stimulated both mouse and human NKT cells producing IFN-g. CD1d tetramers loaded with these compounds bound human and mouse NKT cells, revealing that these compounds are recognized directly by NKT cells. Taken together, TLR signaling and endogenous glycolipid iGb3 are critical for NKT cells activation in response to LPS-containing bacteria and specific microbial glycosylceramides of Gram-negative bacteria that lack LPS can activate NKT cells directly.

References:

1.      Godfrey, D. I. et al. NKT cells: what’s in a name? Nat. Rev. Immunol. 4, 231-237 (2004).

2.      Mattner, J. et al. Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434, 525-529, 2005