Our research focuses on immune responses to viral infections in the central nervous system (CNS), with an emphasis on persistent infections and immune-pathology manifested by demyelination. Neurotropic coronavirus-induced encephalomyelitis is used to investigate how resident CNS cells trigger and modulate immune function. Although innate and adaptive immune responses join forces to control virus, it persists in the CNS at low levels. Our goal is to dissect the contribution of distinct lymphocyte subsets to long-term virus control as well as demyelinating disease. These insights will assist in developing strategies not only to combat acute CNS infections, but also to maintain control of endogenous viruses during immunemodulatory treatment of autoimmune inflammation. Three projects are under way:
1. Characterization of innate immune responses in glia. We are investigating how type I interferon induced antiviral activities (OAS/RNaseL, PKR, IFIT1/2) affect viral control in distinct cell types.
2. Regulation of CNS-infiltrating T cells by inhibitory factors. Our studies revealed that efficient viral control by CD8 T cells is dampened by inhibitory factors but enhanced by CD4 T cells, which are also major effectors of pathology. Efforts are underway to understand the mechanisms underlying CD4 T cell help to CD8 T cells on one side, but enhanced neuronal damage on another.
3. Maintenance of humoral immunity within the CNS. Intrathecal antibody-secreting cells control virus re-emergence during the persistent phase of infection. Various transgenic and knockout mice are used to characterize factors regulating B cell entry, differentiation and maintenance within the CNS.
Dr. Bergmann's research explores how the immune system controls viral infections of the central nervous system (CNS), while minimizing tissue destruction. Her studies evaluate how specialized cells of the CNS respond to virus infection and how these responses contribute to recruitment of protective leukocytes circulating in the blood into the CNS. This work has revealed how various leukocyte populations and their distinct functions interact to control virus at distinct phases of disease. Ongoing research focuses on how specific immune functions can be manipulated to maximize viral control without leading to overt pathology involving neuronal damage.
Marques CP, Kapil P, Hinton DR, Hindinger C, Nutt SL, Ransohoff RM, Phares TW, Stohlman SA, Bergmann CC. 2011. CXCR3-Dependent Plasma Blast Migration to the Central Nervous System during Viral Encephalomyelitis. J Virol 85(13):6136-47.
Savarin C, Stohlman SA, Rietsch AM, Butchi N, Ransohoff RM, Bergmann CC. 2011 MMP9 deficiency does not decrease blood brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis. Glia 59(11):1770-81.
Phares TW, Stohlman SA, Hwang M, Min B, Hinton DR, Bergmann CC. 2012. CD4 T cells promote CD8 T cell immunity at the priming and effector site during viral encephalitis. J Virol86(5):2416-27.
Savarin C, Stohlman SA, Hinton DR, Ransohoff RM, Cua DJ, Bergmann CC. 2012. IFN-gamma protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils. J Neuroinflammation 29;9(1):104.
Kapil P, Butchi NB, Stohlman SA, Bergmann CC. 2012. Oligodendroglia are limited in type I interferon induction and responsiveness in vivo. Glia 60(10):1555-66.