Innate Immune Responses Contribute to Host Defense, Disease, and Repair in Response to Viral Infection of the CNS

Viral infection of the central nervous system (CNS) results in a number of different clinical outcomes ranging from benign infection to life-threatening conditions as well as insidious disease characterized by viral persistence with potential for life-long neurological complications. Importantly, the past 20 years has recognized the emergence of neurotropic viruses that have caused a myriad of clinical problems and raised public awareness of the importance of studying viruses that infect the CNS. We employ infection of susceptible mice with the neurotropic JHM strain of mouse hepatitis virus (JHMV) to better understand the molecular and cellular mechanisms influencing host defense, demyelination, and remyelination. While the adaptive immune response is critical in effectively controlling viral replication as well as contributing to neurodegeneration, the contributions of the innate immune response to these processes is less well understood. We have recently determined that both neutrophils and microglia are important contributors in optimizing host defense following JHMV infection. In addition, we’ve shown that sustained infiltration of neutrophils into the CNS augments demyelination whereas microglia ablation limits the severity of white matter damage and restricts remyelination. We are currently attempting to address the mechanisms by which neutrophils and microglia influence these two separate events.