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Dr. rer. nat. Mirko Kummer
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Research interest:
Current research mainly focuses on the interplay between the alpha-herpesvirus HSV-1 and mature dendritic cells (mDC).
HSV-1 is very successful representative of its family, as almost 90 percent of the population is seropositive for this particular virus. Usually, the virus causes the well known mild lip lesions, but in rare cases also severe symptoms such as encephalitis or keratoconjunctivitis are observed. When this virus meets the most potent antigen presenting cell of the immune system, the mDC, a hide-and-seek begins. As the invader seeks to hide itself from the immune system, the host tries to clear the infection.
In the last years our group reported a number of immune evasion strategies used by HSV-1 to avoid a proper immune response. For example, HSV-1 downregulates CCR7 from mDC thus preventing the cells from migrating to the draining lymphnodes. Furthermore, CD83, a potential costimulatory molecule on the surface of mDCs, is degraded almost completely leading to a clearly diminished stimulatory capacity of the infected cell. In addition, HSV-1 interferes with the STAT1 signalling pathway, probably by reducing IFNGR1 from the cells’ surface. Ongoing projects mainly aim at the identification of additional immune evasion strategies used by HSV-1 following the infection of mDCs.
Another focus lies on the expression and purification of a) recombinant and b) natural soluble CD83 (sCD83). This molecule has been reported to possess a prophylactic and also a therapeutical potential in prevention and treatment of the experimental autoimmune encephalomyelitis (EAE), which is a model for the human multiple sclerosis (MS). Here prokaryotic as well as eukaryotic expression systems together with HPLC techniques are used.
Selected References:
Goldwich A, Prechtel AT, Mühl-Zürbes P, Pangratz NM, Stössel H, Romani N, Steinkasserer A, Kummer M. Herpes simplex virus type I (HSV-1) replicates in mature dendritic cells but can only be transferred in a cell-cell contact-dependent manner. J Leukoc Biol. 2011 Jun;89(6):973-9. Epub 2011 Mar 22.
Staab C, Mühl-Zürbes P, Steinkasserer A, Kummer M. Eukaryotic expression of functionally active recombinant soluble CD83 from HEK 293T cells. Immunobiology. 2010;215(9-10): 849-54
Eisemann J, Prechtel AT, Mühl-Zürbes P, Steinkasserer A, Kummer M.
Herpes simplex virus type I infection of mature dendritic cells leads to reduced LMP7-mRNA-expression levels.
Immunobiology. 2009;214(9-10):861-7. Epub 2009 Jul 19.
Kummer M, Prechtel AT, Mühl-Zürbes P, Turza NM, Steinkasserer A.
HSV-1 upregulates the ARE-binding protein tristetraprolin in a STAT1- and p38-dependent manner in mature dendritic cells.
Immunobiology. 2009;214(9-10):852-60
Kummer, M., Turza, N. M., Muhl-Zurbes, P., Lechmann, M., Boutell, C., Coffin, R. S., Everett, R. D., Steinkasserer, A., and Prechtel, A. T. (2008). Herpes simplex virus type 1 induces CD83 degradation in mature dendritic cells with immediate-early kinetics via the cellular proteasome. Experimental Dermatology 17, 256.
Kummer, M., Turza, N. M., Muhl-Zurbes, P., Lechmann, M., Boutell, C., Coffin, R. S., Everett, R. D., Steinkasserer, A., and Prechtel, A. T. (2007). Herpes simplex virus type 1 induces CD83 degradation in mature dendritic cells with immediate-early kinetics via the cellular proteasome. Journal of Virology 81, 6326-6338.
Elsemann, J., Muehl-Zuerbes, P., Steinkasserer, A., and Kummer, M. (2007). Infection of mature dendritic cells with herpes simplex virus type I interferes with the interferon signaling pathway. Immunobiology 212, 877-886.
Prechtel AT, Turza NM, Theodoridis AA, Kummer M, Steinkasserer A.
Small interfering RNA (siRNA) delivery into monocyte-derived dendritic cells by electroporation.
J Immunol Methods. 2006 Apr 20;311(1-2):139-52. Epub 2006 Mar 6.
