Recognition of bacterial glycosphingolipids by natural killer T cells

Abstract

Natural killer T (NKT) cells constitute a highly conserved T lymphocyte subpopulation that has the potential to regulate many types of immune responses through the rapid secretion of cytokines1,2. NKT cells recognize glycolipids presented by CD1d, a class I-like antigen-presenting molecule. They have an invariant T-cell antigen receptor (TCR) α-chain, but whether this invariant TCR recognizes microbial antigens is still controversial. Here we show that most mouse and human NKT cells recognize glycosphingolipids from Sphingomonas, Gram-negative bacteria that do not contain lipopolysaccharide3,4,5. NKT cells are activated in vivo after exposure to these bacterial antigens or bacteria, and mice that lack NKT cells have a marked defect in the clearance of Sphingomonas from the liver. These data suggest that NKT cells are T lymphocytes that provide an innate-type immune response to certain microorganisms through recognition by their antigen receptor, and that they might be useful in providing protection from bacteria that cannot be detected by pattern recognition receptors such as Toll-like receptor 4.

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Figure 1: Vα14i NKT-cell hybridomas respond to Sphingomonas glycolipids.
Figure 2: Most Vα14i NKT cells bind GSL-1/CD1d tetramers.
Figure 3: In vitro response of non-transformed Vα14i NKT cells to Sphingomonas antigens.
Figure 4: In vivo response of Vα14i NKT cells to bacterial antigens and bacteria.
Figure 5: Human Vα24i NKT cells respond to synthetic Sphingomonas glycolipids.

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Acknowledgements

We thank K. J. L. Hammond for critical reading of the manuscript, and S. Sidobre, L. Sidobre, K. J. L. Hammond and A. Khurana for mCD1d protein. This work was supported by grants from the National Institutes of Health (to M.K., to C-H.W. and to M.T.). Y.K. was supported in part by the Yamada Science Foundation.

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Correspondence to Mitchell Kronenberg.

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Supplementary information

Supplementary Figure S1

This figure shows in vivo activation of V□14i NKT cells after injection of DCs pulsed with GSL-1'sA or S. yanoikuyae. (PDF 39 kb)

Supplementary Figure S2

This figure shows GSL-1'sA does not cause TNF-α production by DCs. (PDF 28 kb)

Supplementary Figure S3

This figure shows TLR4 independent activation of Vα14i NKT cells. (PDF 30 kb)

Supplementary Figure S4

This figure shows TLR independent IFN-γ production by Vα14i NKT cells. (PDF 42 kb)

Supplementary Figure S5

This figure shows IL-12 independent IFN-γ production by Vα14i NKT cells. (PDF 47 kb)

Supplementary Figure S6

This figure shows IL-12 independent IL-4 production by Vα14i NKT cells. (PDF 35 kb)

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Kinjo, Y., Wu, D., Kim, G. et al. Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434, 520–525 (2005). https://doi.org/10.1038/nature03407

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