Role of invariant NKT cells in lipopolysaccharide-induced lethal shock during encephalomyocarditis virus infection.
Viral infections can give rise to secondary bacterial infections. In the present study, we examined the role of invariant natural killer T (iNKT) cells in lipopolysaccharide (LPS)-induced lethal shock during encephalomyocarditis virus (EMCV) infection. Wild-type (WT) mice and Jα18 gene knockout (Jα18 KO) mice were inoculated with EMCV, 5days prior to challenging with LPS. The survival rate of Jα18 KO mice subjected to EMCV and LPS was significantly higher than that of WT mice. TNF-α and nitric oxide (NO) production were increased in WT mice, than that in Jα18 KO mice, after the administration of EMCV and LPS. EMCV infection increased the number of iNKT cells and IFN-γ production by iNKT cells in WT mice. Moreover, EMCV infection enhanced the expression of Toll-like receptor 4 (TLR4) in the lung and spleen. IFN-γ also increased the expression of TLR4 in splenocytes. These findings indicated that EMCV infection activated iNKT cells, and IFN-γ secreted from the iNKT cells up-regulated the expression of TLR4 in various tissues. As a result, EMCV-infected mice were susceptible to LPS and easily developed the lethal shock. In conclusion, iNKT cells were involved in the development of LPS-induced lethal shock during EMCV infection.
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Tatsuya
T
Ando
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. Electronic address: hito@gifu-u.ac.jp.
Hiroyasu
H
Ito
Department of Medical Technology, Kansai University of Health Sciences, 2-11-1 Wakaba, Kumatori, Osaka 590-0482, Japan.
Hirofumi
H
Ohtaki
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Ayumu
A
Kanbe
Division of Animal Experiment, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
Akihiro
A
Hirata
Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Akira
A
Hara
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Mitsuru
M
Seishima
D000818:Animals; D015415:Biomarkers; D018188:Cardiovirus Infections / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000821:virology; D060085:Coinfection; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004686:Encephalomyocarditis virus / Q000276:immunology*; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D012772:Shock, Septic / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide
Encephalomyocarditis virus; Endotoxin shock; Inducible nitric oxide synthase; Natural killer T cell; Toll-like receptor 4