Role of nucleotide-binding oligomerization domain-like receptor 3 in mice with herpes simplex virus type Ⅰ encephalitis

OBJECTIVE To investigate the role of nucleotide-binding oligomerization structural domain-like receptors (NODR) 3 in mice with herpes simplex virus type Ⅰ encephalitis.

METHODS Sixty SPF-grade male mice were divided into 30 NLRP3 wild-type (WT) mice and NODR3 knockout (KO) mice, and NLRP3 wild-type mice were further divided into WT-Control group and WT-Model group, and NLRP3 knockout mice were divided into KO-Control group and KO-Model group; Mice in the WT-Model and KO-Model groups were inoculated with herpes simplex virus type Ⅰ (HSVⅠ) suspension to establish the viral encephalitis (HSE) Model. After 5 days of inoculation, the white blood cell (WBC) count and virus titer in the cerebrospinal fluid of mice were detected, the brain tissue moisture content and oxidative stress related index levels were determined, and the relative expression of NOD-like receptor-related proteins, oxidative stress-related proteins, and T cell subset specific cytokines proteins in the brain tissue were detected by Western blotting.

RESULTS The mice in the WT-control group and KO-control group were in good condition, while the mice in the WT-model group and KO-model group showed redness, swollen and ulcerated corners of the eyes, unresponsiveness, and convulsions, etc.. Compared with the WT-control group and KO-control group, the mice in the WT-model and KO-model groups had increased white blood cell (WBC) counts in cerebrospinal fluid, elevated wet weight and water content of brain tissue, elevated expression of malondialdehyde (MDA), interferon (IFN)-γ, interleukin (IL)-4, IL-17, and forkhead frame protein (FOX) P3, decreased total antioxidant capacity (T-AOC) and superoxide dismutase (SOD), and decreased level of nuclear factor E2-related factor (Nrf) 2, heme oxidase (HO)-1, and quinone oxidoreductase (NQO)-1. Virus titer, brain tissue wet weight and water content, MDA, IFN-γ, IL-4, IL-17, FOXP3 were lower in the KO-model group than those in the WT-model group, and T-AOC, SOD, Nrf2, HO-1, NQO-1 were higher than those in the WT-model group (P < 0.05). NOD-like receptor-related proteins were not detected in the brain tissues of mice in the KO-control and KO-model groups, and the expression levels of NLRP3, ACS, and Caspase-1 in the WT-model group were higher than those in the WT-control group (P < 0.05).

CONCLUSION The expression of NOD-like receptors might be related to the level of oxidative stress in brain tissues, and its high expression in mice of the HSE Model group could activate oxidative stress injury and participate in cellular immune regulation.