Role of CD40 Expressed by the Glial Cells in the Pathogenesis of Mouse Hepatitis Virus

Patil, Neha (2015) Role of CD40 Expressed by the Glial Cells in the Pathogenesis of Mouse Hepatitis Virus. Masters thesis, Indian Institute of Science Education and Research Kolkata.

PDF (MS dissertation of Neha Patil (10MS60)) MS_thesis_Patil_Neha_10MS60.pdf - Submitted Version Restricted to Repository staff only Download (1MB)

Abstract

CD40, belonging to the tumor necrosis factor superfamily, is a membrane protein receptor on the antigen presenting cells and is necessary as a mediator in various immune and inflammatory responses, especially in T cell dependent humoral immunity. The ligand of CD40, known as CD40L or CD154 is a member of TNF superfamily and is generally expressed on the activated T cells. The interaction between these two molecules is responsible for immune response regulation, B cell proliferation and in viral defense among many others. Under pathogenic attack, their altered regulation has been seen in various autoimmune diseases. Earlier studies have shown that CD40-CD40L interaction along with cytokines is responsible for microglial activation and this is marked by upregulation in level of CD40 expression on the microglia. It has been seen that this CD40 expression is required for microglia’s two step activation process during the CNS autoimmune inflammation. Microglia are vital in maintaining the neuronal microenvironment and thus in normal brain function. Viral models help in mimicking certain brain pathology in case of diseases like multiple sclerosis. It is seen that microglia are heavily activated in MHV induced neuroinflammation and the lab’s previous affymetrix microarray data shows that CD40 acts as an interlink between the innate and adaptive immune system. In this study, we used MHV-A59 strain for studying the regulation of CD40 expression on neuronal (N2a) and microglial (N9) cells. The cells were characterized by immunofluorescence, and then infected and their total protein and RNA were isolated. We found the upregulation in CD40 expression through western blotting and RT-PCR data in N9 cells. Further studies are going on for studying the effect of MHV infection on N2a cells. Also, background studies (as a reading project) on the structures of CD40 and CD154 and their involvement in various pathways in viral induced neuroinflammation are being carried to determine their role in MHV induced neuroinflammation.

Actions (login required)

View Item