A3 - Regulation of the T cell activity in the course of bacterial liver infections
Prof. Dr. rer. nat. Hans-Willi Mittrücker
Institut für Immunologie, Diagnostikzentrum
Universitätsklinikum Hamburg Eppendorf
Tel.: +49-40 -7410-57922
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 SecondsVideoarchivonline 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.
Schneider M, Schumacher V, Lischke T, Lücke K, Meyer-Schwesinger C, Velden J, Koch-Nolte F, Mittrücker HW
CD38 is expressed on inflammatory cells of the intestine and promotes intestinal inflammation
PLoS One. 2015 May 4;10(5):e0126007. doi: 10.1371/journal.pone.0126007. eCollection 2015.
Yan I, Schwarz J, Lücke K, Schumacher N, Schumacher V, Schmidt S, Rabe B, Saftig P, Donners M, Rose-John S, Mittrücker HW, Chalaris A
ADAM17 controls IL-6 signaling by cleavage of the murine IL-6Rα from the cell surface of leukocytes during inflammatory responses
J Leukoc Biol. 2015 Nov 11. pii: jlb.3A0515-207R.[Epub ahead of print]
Wroblewski R, Armaka M, Kondylis V, Pasparakis M, Walczak H, Mittrücker HW, Schramm C, Lohse AW, Kollias G, Ehlken H
Opposing Role of Tumor Necrosis Factor Receptor 1 Signaling in T Cell Mediated Hepatitis and Bacterial Infection In Mice
Hepatology. 2016 Mar 17. doi: 10.1002/hep.28551. [Epub ahead of print]