CD4+ T cells regulate Mouse Hepatitis Virus induced activation of microglia

Abstract

Abstract Multiple Sclerosis (MS) is a human neurological disease characterised by neuroinflammatory demyelination and axonal loss. Studies in MS are focussed to understand the process of demyelination driven by B/T lymphocytes, but we have limited knowledge about direct virus-induced neural cell dystrophy and the role of innate immunity in MS. Our studies employ Mouse Hepatitis Virus (MHV) induced neuroinflammatory model to understand microglia-mediated myelin stripping as a mechanism of demyelination. Microglia are the CNS resident macrophages that lie at the intersection of immune response and neurodegenerative process. They control the initiation, progression and resolution of neuroinflammation in the CNS. One of our studies in MHV model demonstrated that in the absence of CD4+ T cells, mice are more susceptible to acute encephalitis and chronic demyelination. In order to understand the mechanism of anti-viral immune response, we have investigated the role of microglia upon CD4+ T cell modulation. Results from our studies showed that a higher number of Iba1+ microglial cells persist in the brain parenchyma of CD4−/− mice at the chronic infection stage in comparison to the WT mice. Real-time qPCR screening of inflammatory markers like IL6, IL10, IL12, CXCL10, CCL5, CD86 and CD163 presented a consistent proinflammatory microenvironment in the CNS and comparative lower expression of Btk1 and Arg1 in the brains of CD4−/− mice. In conclusion, our findings propose that further in vitro and in vivo studies are necessary to understand the role of CD4+ T cell activation and maturation which might help in favouring a shift towards adaptive immunity, differential microglial activation, viral clearance and maintaining neural homeostasis.