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Thomas Lane, PhD
University of Utah
Title: Innate immune responses contribute to host defense, disease and repair in a model of viral-induced neurologic disease
Date: Monday, March 11, 2019
Location: Herklotz Conference Center, Center for Neurobiology of Learning and Memory
Abstract: 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 driving white matter demyelination, the contributions of the innate immune response to these processes is less well understood. We have recently determined that microglia are critical in enhancing host defense following JHMV infection as well as restricting the severity of demyelination by influencing the immunological landscape within the CNS. Moreover, sustained neutrophil infiltration into the CNS of JHMV-infected mice leads to increased demyelination through mechanisms that may include release of neutrophil extracellular traps (NETs) and reactive nitrogen/oxygen species. Finally, we have identified an important chemokine signaling pathway that influences maturation of oligodendroglia into mature myelin-producing oligodendrocytes and this influences remyelination in JHMV-infected mice. Collectively, these findings may offer insight into new strategies to develop novel therapies that impede disease progression and promote repair.