A3 Regulation of antibacterial immune responses in the liver


Principal Investigator:
Prof. Dr. rer. nat. Hans-Willi Mittrücker
Institut für Immunologie, Diagnostikzentrum
Universitätsklinikum Hamburg Eppendorf
Martinistr. 52
20246 Hamburg
Tel.: +49-40 -7410-57922
Fax: +49-40-7410-54243
E-Mail: h.mittruecker@uke.de

Project description
The liver is a target organ for several pathogens. Control of some these pathogens depends on the cytokine interleukin-6 (IL-6). IL-6 supports the innate protection against pathogens but it also regulates induction and differentiation processes of adaptive immune responses.
The mechanisms of IL-6-mediated control of pathogens are only partially understood. In addition IL-6 exerts not only protective functions, the cytokine is also involved in formation and maintenance of chronic inflammatory diseases. Thus, a detailed understanding of the function of IL-6 is crucial for the development of therapeutic strategies that rely on the modulation of IL-6 activity.

A3 in 60 SecondsVideoarchiv

online seit 17.07.2014

During the 1st funding period, we could demonstrate a role for IL-6 in the control of liver infection with Listeria monocytogenes. IL-6-mediated control during the first days of infection almost exclusively depended on the activation of cells by classical IL-6 signaling via the membrane bound IL-6 receptor α-chain (IL-6Rα). IL-6 trans-signaling via soluble IL-6/IL-6Rα complexes had only a neglectible role. IL-6Rα was also actively shed from the surface of different leucocytes during infection. Therefore, the activity of IL-6 was controlled via the level of production as well as the mode of recognition by different target cells.
In the current funding period, we aim to identify the cells responsible for IL-6 production during different phases of infection and to analyze the impact of IL-6 classical and trans-signaling on the response of different immune cells. Finally, we will characterize the proteases responsible for IL-6Rα shedding and the general function of the proteases in the immune response against bacterial infections.

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CD38 is expressed on inflammatory cells of the intestine and promotes intestinal inflammation
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