Cutting Edge: the Mechanism of Invariant NKT Cell Responses to Viral Danger Signals

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2008 Sep 20

PMID 18802047

Citations 111

Authors

Aaron J Tyznik

Emmanuel Tupin

Niranjana A Nagarajan

Min J. Her

Chris A Benedict

Mitchell Kronenberg

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Immune surveillance of cytomegalovirus in tissues.

Mihalic A, Zeleznjak J, Lisnic B, Jonjic S, Juranic Lisnic V, Brizic I Cell Mol Immunol. 2024; 21(9):959-981.

PMID: 39134803 PMC: 11364667. DOI: 10.1038/s41423-024-01186-2.

invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies.

Boonchalermvichian C, Yan H, Gupta B, Rubin A, Baker J, Negrin R Front Transplant. 2024; 3:1353803.

PMID: 38993780 PMC: 11235242. DOI: 10.3389/frtra.2024.1353803.

-the struggles and battles of innate-like effector T lymphocytes with microbes.

Joyce S, Okoye G, Driver J Front Immunol. 2023; 14:1117825.

PMID: 37168859 PMC: 10165076. DOI: 10.3389/fimmu.2023.1117825.

CD8 T-cell immunity orchestrated by iNKT cells.

Qin Y, Bao X, Zheng M Front Immunol. 2023; 13:1109347.

PMID: 36741397 PMC: 9889858. DOI: 10.3389/fimmu.2022.1109347.

Research progress of the engagement of inorganic nanomaterials in cancer immunotherapy.

Peng T, Xu T, Liu X Drug Deliv. 2022; 29(1):1914-1932.

PMID: 35748543 PMC: 9246104. DOI: 10.1080/10717544.2022.2086940.

References

Biron C, Brossay L . NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol. 2001; 13(4):458-64. DOI: 10.1016/s0952-7915(00)00241-7. View

van Dommelen S, Tabarias H, Smyth M, Degli-Esposti M . Activation of natural killer (NK) T cells during murine cytomegalovirus infection enhances the antiviral response mediated by NK cells. J Virol. 2003; 77(3):1877-84. PMC: 140953. DOI: 10.1128/jvi.77.3.1877-1884.2003. View

Andrews D, Scalzo A, Yokoyama W, Smyth M, Degli-Esposti M . Functional interactions between dendritic cells and NK cells during viral infection. Nat Immunol. 2002; 4(2):175-81. DOI: 10.1038/ni880. View

Brigl M, Bry L, Kent S, Gumperz J, Brenner M . Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat Immunol. 2003; 4(12):1230-7. DOI: 10.1038/ni1002. View

Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K . Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A. 2004; 101(10):3516-21. PMC: 373494. DOI: 10.1073/pnas.0400525101. View

Krug A, French A, Barchet W, Fischer J, Dzionek A, Pingel J . TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity. 2004; 21(1):107-19. DOI: 10.1016/j.immuni.2004.06.007. View

Suzuki Y, Wakita D, Chamoto K, Narita Y, Tsuji T, Takeshima T . Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing type 1 innate immunity. Cancer Res. 2004; 64(23):8754-60. DOI: 10.1158/0008-5472.CAN-04-1691. View

Kinjo Y, Kronenberg M . V alpha14 i NKT cells are innate lymphocytes that participate in the immune response to diverse microbes. J Clin Immunol. 2005; 25(6):522-33. DOI: 10.1007/s10875-005-8064-5. View

Montoya C, Jie H, Al-Harthi L, Mulder C, Patino P, Rugeles M . Activation of plasmacytoid dendritic cells with TLR9 agonists initiates invariant NKT cell-mediated cross-talk with myeloid dendritic cells. J Immunol. 2006; 177(2):1028-39. DOI: 10.4049/jimmunol.177.2.1028. View

10.

Van Kaer L, Joyce S . Viral evasion of antigen presentation: not just for peptides anymore. Nat Immunol. 2006; 7(8):795-7. DOI: 10.1038/ni0806-795. View

11.

Shresta S, Sharar K, Prigozhin D, Beatty P, Harris E . Murine model for dengue virus-induced lethal disease with increased vascular permeability. J Virol. 2006; 80(20):10208-17. PMC: 1617308. DOI: 10.1128/JVI.00062-06. View

12.

Tupin E, Kronenberg M . Activation of natural killer T cells by glycolipids. Methods Enzymol. 2006; 417:185-201. DOI: 10.1016/S0076-6879(06)17014-7. View

13.

Nagarajan N, Kronenberg M . Invariant NKT cells amplify the innate immune response to lipopolysaccharide. J Immunol. 2007; 178(5):2706-13. DOI: 10.4049/jimmunol.178.5.2706. View

14.

Bendelac A, Savage P, Teyton L . The biology of NKT cells. Annu Rev Immunol. 2006; 25:297-336. DOI: 10.1146/annurev.immunol.25.022106.141711. View

15.

Van Kaer L . NKT cells: T lymphocytes with innate effector functions. Curr Opin Immunol. 2007; 19(3):354-64. DOI: 10.1016/j.coi.2007.03.001. View

16.

Tupin E, Kinjo Y, Kronenberg M . The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol. 2007; 5(6):405-17. DOI: 10.1038/nrmicro1657. View

17.

Paget C, Mallevaey T, Speak A, Torres D, Fontaine J, Sheehan K . Activation of invariant NKT cells by toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids. Immunity. 2007; 27(4):597-609. DOI: 10.1016/j.immuni.2007.08.017. View

18.

Velazquez P, Cameron T, Kinjo Y, Nagarajan N, Kronenberg M, Dustin M . Cutting edge: activation by innate cytokines or microbial antigens can cause arrest of natural killer T cell patrolling of liver sinusoids. J Immunol. 2008; 180(4):2024-8. DOI: 10.4049/jimmunol.180.4.2024. View

19.

Raftery M, Winau F, Giese T, Kaufmann S, Schaible U, Schonrich G . Viral danger signals control CD1d de novo synthesis and NKT cell activation. Eur J Immunol. 2008; 38(3):668-79. DOI: 10.1002/eji.200737233. View

20.

Schneider K, Loewendorf A, De Trez C, Fulton J, Rhode A, Shumway H . Lymphotoxin-mediated crosstalk between B cells and splenic stroma promotes the initial type I interferon response to cytomegalovirus. Cell Host Microbe. 2008; 3(2):67-76. PMC: 2703178. DOI: 10.1016/j.chom.2007.12.008. View