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 J alpha 18 gene knockout (1 alpha 18 KO) mice were inoculated with EMCV, 5 days prior to challenging with LPS. The survival rate of J alpha 18 KO mice subjected to EMCV and LPS was significantly higher than that of WT mice. TNF-alpha and nitric oxide (NO) production were increased in WT mice, than that in J alpha 18 KO mice, after the administration of EMCV and LPS. EMCV infection increased the number of iNKT cells and IFN-gamma 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-gamma also increased the expression of TLR4 in splenocytes. These findings indicated that EMCV infection activated iNKT cells, and IFN-gamma 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. (C) 2016 Elsevier GmbH. All rights reserved.