Nucleotide-Binding Oligomerization Domain 1 (NOD1) regulates microglia activation in Pseudorabies Virus Infection

Abstract

Abstract The primary cause of viral encephalitis is the invasion of the central nervous system (CNS) by the virus, leading to neuroinflammation, which poses a significant threat to global public health. Microglia, as CNS-resident macrophages, play a crucial role in neuroinflammation and are often identified as the preferred target for the prevention or treatment of viral encephalitis. Nucleotide-binding oligomerization domain 1 (NOD1) is a pattern recognition receptor associated with various human inflammatory diseases. In this study, we used pseudorabies virus (PRV) as a model to investigate the regulation of microglial responses during viral encephalitis and explored whether NOD1 suppressed neuroinflammation by regulating microglial activation. Cellular experiments revealed microglia activation accompanied by cell migration, characteristic morphological changes, phagocytosis, inflammatory cytokine production, and antigen presentation. Subsequently, we studied the impact of NOD1 on PRV-induced microglia activation. Both in vitro and in vivo results demonstrated that PRV infection upregulated the mRNA and protein expression of NOD1. Modulation of NOD1 expression, either through inhibition or overexpression, resulted in a corresponding reduction or enhancement of the JNK and NF-κB signaling pathways, regulating microglial activation and the inflammatory response induced by PRV. BACKGROUND Viral encephalitis is an acute inflammatory process resulting from viral infections in the CNS. Microglia, as the primary effectors of inflammation in the CNS, play a crucial role. Notably, NOD1/RIP2 signalling is implicated in the initiation of inflammatory responses to viruses. Our study offers novel perspectives for developing protective strategies against neuroinflammation by elucidating the NOD1/RIP2-mediated regulation of microglia. Furthermore, it identifies NOD1 as a potential target for mitigating microglia hyperactivation.