期刊
JOURNAL OF IMMUNOLOGY
卷 191, 期 11, 页码 5646-5654出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1301412
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资金
- Crohn and Colitis Foundation of Canada
- Canada Foundation for Innovation Physical Infrastructure Grant [29186]
- Canadian Institutes of Health Research grant
- Canadian Institutes of Health Research Banting and Best Doctoral Research Award
- Canadian Institutes of Health Research New Investigator Salary Award [MSH-122783]
Invariant NKT (iNKT) cells act at the crossroad between innate and adaptive immunity and are important players in the defense against microbial pathogens. iNKT cells can detect pathogens that trigger innate receptors (e.g., TLRs, Rig-I, Dectin-1) within APCs, with the consequential induction of CD1d-mediated Ag presentation and release of proinflammatory cytokines. We show that the cytosolic peptidoglycan-sensing receptors Nod1 and Nod2 are necessary for optimal IFN-gamma production by iNKT cells, as well as NK cells. In the absence of Nod1 and Nod2, iNKT cells had a blunted IFN-gamma response following infection by Salmonella enterica serovar Typhimurium and Listeria monocytogenes. For Gram-negative bacteria, we reveal a synergy between Nod1/2 and TLR4 in dendritic cells that potentiates IL-12 production and, ultimately, activates iNKT cells. These findings suggest that multiple innate pathways can cooperate to regulate iNKT cell activation during bacterial infection.
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