Dysregulated Levels of TLRs, Cytokines and Chemokines in mouse brain infected with Japanese encephalitis virus via intracerebral route and tail vein route showing worst disease outcome

Despite the availability of vaccines, Japanese encephalitis (JE) is the leading cause of viral encephalitis related death each year in South East Asian region. As there is incomplete understanding on the pathogenesis of Japanese encephalitis virus (JEV), thousands of deaths are reported annually due to JEV infection in these regions. JEV also causes high morbidity in humans, leading to permanent neurological deficits, even in those who survive. In our recent research study45, we explored the role of specific cytokines, chemokines and TLRs through in vitro studies. We demonstrated that exaggerated levels of TLRs (2,4 &9), cytokines (IL-6, IL-17 and chemokines (MCP-1, RANTES) in BV2 and Neuro2A cell lines were associated with worst outcome45. In present manuscript we assessed the roles of those TLRs, cytokines and chemokines in the central nervous system (CNS) of the mouse brain post JEV infection by intracerebral and tail vein route. For this, we developed the mouse model of encephalitis by injecting the GP-78 (JEV a neurovirulent strain) virus through IC and TV route. We noticed the upregulated levels of some specific TLRs, cytokines and chemokines in mouse brain following IC and TV challenge at different days post JEV infection. The increased levels of some specific TLRs, cytokines and chemokines have worst outcome in disease progression and tissue pathology at later stage of infection.