Glycolipids from the gut symbiont Bacteroides fragilis are agonists for natural killer T cells and induce their regulatory differentiation

G Cameron; T Nguyen; M Ciula; SJ Williams; DI Godfrey

Journal article

Glycolipids from the gut symbiont Bacteroides fragilis are agonists for natural killer T cells and induce their regulatory differentiation

G Cameron, T Nguyen, M Ciula, SJ Williams, DI Godfrey

Chemical Science | Published : 2023

DOI: 10.1039/d3sc02124f

Abstract

Natural Killer T (NKT) cells are a lipid-antigen reactive T cell subset that is restricted to the antigen presenting molecule CD1d. They possess diverse functional properties that contribute to inflammatory and regulatory immune responses. The most studied lipid antigen target for these T cells is α-galactosylceramide (αGC). The commensal organism Bacteroides fragilis (B. fragilis) produces several forms of αGC, but conflicting information exists about the influence of these lipids on NKT cells. Herein, we report the total synthesis of a major form of αGC from B. fragilis (Bf αGC), and several analogues thereof. We confirm the T cell receptor (TCR)-mediated recognition of these glycolipids b..

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University of Melbourne Researchers

Garth Cameron Author

Marcin Ciula Author

Spencer Williams Author

Dale Godfrey Author

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Grants

Awarded by Harvard University

Funding Acknowledgements

This work was supported by grants from the Australian Research Council (DP210100233, DP210100235) and the National Health and Medical Research Council of Australia (NHMRC; 1113293, 1140126). D. I. G. was supported by an NHMRC Senior Principal Research Fellowship (1117766) and subsequently, an NHMRC Investigator Award (2008913). We are grateful to Paul Savage (Brigham Young University, UT, USA) for providing aGC/PBS-44. We thank staff from the flow cytometry facility at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne. David Hay for writing up award to T. Nguyen. 5-OP-RU was kindly provided by David Fairlie (University of Queensland). Jon Clardy (Harvard University) is thanked for providing the proton-NMR spectrum of authentic B. fragilis aGC.