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SciLifeLab The Svedberg seminar series 2014-04-14

Allan Randrup Thomsen

Department for International Health, Immunology and Microbiology, Copenhagen University, Copenhagen, Denmark

Allan Randrup Thomsen took medical degree 1980 at University of Copenhagen, where he some years later also became doctor of Medical Sciences. As assistant professor at University of Copenhagen he visited 1987 Rensselaer Polytechnic Institute, Troy, New Yourk. Since 2004, Allan Randrup Thomsen is full professor in Experimental Virology, at the Institute of International Health, Immunology and Microbiology, University of Copenhagen.

Allan Randrup Thomsen extensive scientific work, published in over 140 international scientific papers, is primarily focused to virus/host interplay. To understand molecular interactions necessary for the generation of efficient and sustained antiviral immune response, his group also works on development of efficient vaccines against sever and devastating pathogens.

Cytokine regulation of virus-induced inflammation in the CNS – lessons from a murine model

Intracerebral infection with lymphocytic choriomeningitis virus (LCMV) induces a severe meningoencephalitis from which immunocompent mice die about 8 days later. In order to understand how viral infection of the CNS is handled by the host immune system, we have studied the role of innate signaling pathways and cytokines in regulating the inflammatory response in this organ. Our results indicate that as yet undefined pattern recognition receptors detect (a) viral signature(s). This causes the activation of IRF3 and/or IRF7, resulting in the production of Type I IFN and up-regulation of multiple interferon-stimulated genes (ISGs) including CXCL10 and IRF7 itself. This is different from recognition of peripheral infection with this virus, where presence of IRF7 is mandatory for an IFN-dependent response. Moreover, even though the activation of ISGs does not require IRF7, other components of the IFN-induced transcriptome critically relies on this molecule. The release of CXCL10 attracts virus-specific CD8 T cells, which through release of type II IFN exert a positive feed-back on the local inflammatory response. Interestingly, type II IFN also causes the up-regulation of suppressors of cytokine signaling (SOCS) 1 and 3 in resident cells of the CNS. Thus, our studies have revealed both pro- and anti-inflammatory components of a complex cytokine network regulating LCMV-induced inflammation of the CNS.

Host: Mirjana Grujic