Cutting edge: the mechanism of invariant NKT cell responses to viral danger signals.
Invariant NK T (iNKT) cells influence the response to viral infections, although the mechanisms are poorly defined. In this study we show that these innate-like lymphocytes secrete IFN-gamma upon culture with CpG oligodeoxynucleotide-stimulated dendritic cells (DCs) from mouse bone marrow. This requires TLR9 signaling and IL-12 secretion by the activated DCs, but it does not require CD1d expression. iNKT cells also produce IFN-gamma in response to mouse CMV infection. Their mechanism of mouse CMV detection is quite similar to that of CpG, requiring both TLR9 signaling and IL-12 secretion, while the need for CD1d expression is relatively minor. Consequently, iNKT cells have the ability to respond to a variety of microbes, including viruses, in an Ag-independent manner, suggesting they may play a broad role in antipathogen defenses despite their limited TCR repertoire.
Tyznik
Aaron J
AJ
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Tupin
Emmanuel
E
Nagarajan
Niranjana A
NA
Her
Min J
MJ
Benedict
Chris A
CA
Kronenberg
Mitchell
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000276:immunology* / Q000472:pathogenicity*; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000502:physiology
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9
Curr Opin Immunol. 2001 Aug;13(4):458-64
11498302
J Virol. 2003 Feb;77(3):1877-84
12525622
Nat Immunol. 2003 Feb;4(2):175-81
12496964
Nat Immunol. 2003 Dec;4(12):1230-7
14578883
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3516-21
14993594
Immunity. 2004 Jul;21(1):107-19
15345224
Cancer Res. 2004 Dec 1;64(23):8754-60
15574787
J Clin Immunol. 2005 Nov;25(6):522-33
16380816
J Immunol. 2006 Jul 15;177(2):1028-39
16818759
Nat Immunol. 2006 Aug;7(8):795-7
16855602
J Virol. 2006 Oct;80(20):10208-17
17005698
Methods Enzymol. 2006;417:185-201
17132506
J Immunol. 2007 Mar 1;178(5):2706-13
17312112
Annu Rev Immunol. 2007;25:297-336
17150027
Curr Opin Immunol. 2007 Jun;19(3):354-64
17428648
Nat Rev Microbiol. 2007 Jun;5(6):405-17
17487145
Immunity. 2007 Oct;27(4):597-609
17950005
J Immunol. 2008 Feb 15;180(4):2024-8
18250405
Eur J Immunol. 2008 Mar;38(3):668-79
18253929
Cell Host Microbe. 2008 Feb 14;3(2):67-76
18312841
J Virol. 2008 May;82(9):4308-19
18287231
Curr Top Microbiol Immunol. 2006;298:183-206
16329187