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.
Puntambekar SS, Hinton DR, Yin X, Savarin C, Bergmann CC, Trapp BD, Stohlman SA. (2015) Interleukin-10 is a critical regulator of white matter lesion containment following viral induced demyelination. Glia Jun 30, Epub ahead of print. PMID: 26132901
Butchi N, Kapil P, Puntambekar S, Stohlman SA, Hinton DR, Bergmann CC. (2015) Myd88 Initiates Early Innate Immune Responses and Promotes CD4 T Cells during Coronavirus Encephalomyelitis. J Virol 89(18):9299-312. PMID: 26136579; PMCID: PMC4542380
Savarin C, Hinton DR, Valentin-Torres A, Chen Z, Trapp BD, Bergmann CC, Stohlman SA. (2015) Astrocyte response to IFN-γ limits IL-6-mediated microglia activation and progressive autoimmune encephalomyelitis. J Neuroinflammation 12:79. PMID: 25896970; PMCID: PMC4410573
Hwang M, Phares TW, Hinton DR, Stohlman SA, Bergmann CC, Min B. (2014) Distinct CD4 T cell effects on primary versus recall CD8 T cell responses during viral encephalomyelitis. Immunology 144:374-86. PMID: 25187405; PMCID: PMC4557674
de Aquino MT, Kapil P, Hinton DR, Phares TW, Puntambekar SS, Savarin C, Bergmann CC, Stohlman SA. (2014) IL-27 limits central nervous system viral clearance by promoting IL-10 and enhances demyelination. J Immunol 193(1):285-94. PMID: 24890725; PMCID: PMC4067872
Phares TW, DiSano KD, Stohlman SA, Bergmann CC. (2014) Progression from IgD+ IgM+ to isotype-switched B cells is site specific during coronavirus-induced encephalomyelitis. J Virol 88(16):8853-67. PMID: 24872583; PMCID: PMC4136247
Kapil P, Stohlman SA, Hinton DR, Bergmann CC. (2014) PKR mediated regulation of inflammation and IL-10 during viral encephalomyelitis. J Neuroimmunol 270(1-2):1-12. PMID: 24642385; PMCID: PMC4019976
Butchi NB1, Hinton DR, Stohlman SA, Kapil P, Fensterl V, Sen GC, Bergmann CC. (2014) Ifit2 deficiency results in uncontrolled neurotropic coronavirus replication and enhanced encephalitis via impaired alpha/beta interferon induction in macrophages. J Virol 88(2):1051-64. PMID: 24198415; PMCID: PMC3911674
de Aquino MT, Puntambekar SS, Savarin C, Bergmann CC, Phares TW, Hinton DR, Stohlman SA. (2013) Role of CD25(+) CD4(+) T cells in acute and persistent coronavirus infection of the central nervous system. Virology 447(1-2):112-20. PMID: 24210105; PMCID: PMC3906923
Savarin C, Bergmann CC, Hinton DR, Stohlman SA. (2013) MMP-independent role of TIMP-1 at the blood brain barrier during viral encephalomyelitis. ASN Neuro 5(5):e00127. PMID: 24156369; PMCID: PMC3840398
Phares TW, DiSano KD, Hinton DR, Hwang M, Zajac AJ, Stohlman SA, Bergmann CC. (2013) IL-21 optimizes T cell and humoral responses in the central nervous system during viral encephalitis. J Neuroimmunol 263(1-2):43-54. PMID: 23992866; PMCID: PMC3796038
Phares TW, Stohlman SA, Bergmann CC. (2013) Intrathecal humoral immunity to encephalitic RNA viruses. Viruses 5(2):732-52. PMID: 23435240; PMCID: PMC3640523
Phares TW, Stohlman SA, Hinton DR, Bergmann CC. (2013) Astrocyte-derived CXCL10 drives accumulation of antibody-secreting cells in the central nervous system during viral encephalomyelitis. J Virol 87(6):3382-92. PMID: 23302888; PMCID: PMC3592145