Our research investigates interactions between the central nervous system (CNS) and immune responses to microbial infection. Studies specifically focus on the communication between T cells, B cells, and resident cells in the central nervous system as a site for viral persistence. The disease model centers on a neurotropic coronavirus infection in rodents, which induces an immune mediated demyelinating disease resembling multiple sclerosis (MS). Both adaptive and innate immune responses are required to control virus replication in the CNS, yet virus persists at low levels in the presence of virus specific lymphocytes. A major interest is to uncover downmodulatory mechanisms leading to persistent infection. We are thus analyzing regulation of distinct innate and adaptive antiviral functions throughout the disease course to identify factors beneficial for viral control but potentially harmful to neurologic function. The ultimate goals are to better understand glial cell reactions to inflammation and develop novel strategies to offset neurological and autoimmune disorders potentially associated with acute and persistent microbial infections in the CNS. Using a variety of mice either genetically impaired in antiviral functions or transgenic for marker genes in specific cell types, present studies focus on three major areas:
1. Distinguishing effects of type I and type II IFN responses on viral spread in distinct resident CNS cell types, as well as on T cell responses.
2. Regulation of antigen presentation and immune modulating ligands by glia cells during infection in vivo. These studies comprise analysis of IFN responsiveness and induction of genes associated with antigen processing and presentation.
3. Characterization of signals which mediate ongoing immune responses, specifically maintenance of B cells and immunoglobulin secretion, which are common hallmarks following encephalitic CNS infections and MS.
Stohlman, SA, DR Hinton, B Parra, R Atkinson, CC Bergmann. CD4 T cells contribute to virus control and pathology following CNS infection by neurotropic mouse hepatitis virus. J. Virol. [Epub ahead of print] 2008. [PubMed]
Malone KE, SA Stohlman, C Ramakrishna, W Macklin, CC Bergmann. Induction of class I antigen processing components in oligodendroglia and microglia during viral encephalomyelitis. Glia 56(4):426-35. 2008. [PubMed]
Ireland DC, SA Stohlman, DR.Hinton, R Atkinson, CC Bergmann. Type 1 Interferons are Essential in Controlling Neurotropic Coronavirus Infection irrespective of functional CD8 T cells. J. Virol. 82(1):300-10. 2008. [PubMed]
Bergmann, CC, TE Lane and SA Stohlman. Coronavirus infection of the CNS: Host-virus standoff. Nature Reviews Microbiol. 4:121-132. 2006. [PubMed]
Tschen, S-I, C Ramakrishna, R Atkinson, DR Hinton, SA Stohlman, CC Bergmann. Virus CNS infection diverts homing of antibody secreting cells from lymphoid organs to the CNS. Eur. J. Immunol. 36:603-612. 2006. [PubMed]
Ramakrishna, C, RA Atkinson, SA Stohlman, CC Bergmann. Vaccine Induced Memory CD8+ T Cells Cannot Prevent CNS Viral Persistence and Reactivation. J. Immunol. 176:3062-3069. 2006. [PubMed]