Institute of Medical Microbiology and Hygiene, University Medical Center of Freiburg
We are particularly interested in the function of ILC in the defence of mucosal surfaces. Data on these functions are available for some surfaces (intestine, lung) and some pathogens. The female genital tract is a large mucosal surface area and a frequent entry site for pathogens. ILC have been described at this site. It seems likely that they partake in the reaction against infecting pathogens but this has not been tested. We are investigating the role of ILC in the infection with Chlamydia muridarum in mice (a model for infection with C. trachomatis in women). During this infection, a strong myeloid and T cell response is well documented. Upon resolution of the infection, tissue damage is a frequent result, typically in the form of fibrosis in the oviducts and uterus. We find a strong response of ILC to the infection of mice with C. muridarum and are documenting their role in immune response, bacterial clearance, tissue damage and immunity.
Fischer, S.F., Vier, J., Kirschnek, S., Klos, A., Hess, S., Ying, S. and Häcker, G. (2004) Chlamydia inhibit host cell apoptosis by degradation of pro-apoptotic BH3-only proteins. J Exp Med., 200:905-16.
Paschen, S., Christian, J. G., Vier, J., Schmidt, F., Walch, A., Ojcius, D. M. and Häcker. G. (2008) Cytopathicity of Chlamydia infection can be largely reproduced by expressing a single chlamydial gene, Chlamydial Protease-like Activity Factor. J Cell Biol, 182(1):117-27
Ying, S., Pettengill, M., Latham, E.R., Walch, A., Ojcius, D.M. and Häcker, G. (2008) Premature apoptosis of Chlamydia-infected cells disrupts chlamydial development. J. Infect. Dis., 198(10):1536-44
Christian, J.G., Vier, J., Paschen, S.A. and Häcker G. (2010) Cleavage of the NF-B-family protein p65/RelA by the chlamydial protease chlamydial protease-like activity factor (CPAF) impairs pro-inflammatory signalling in cells Infected with chlamydiae. J Biol Chem., 285(53):41320-7.
Christian, J. G., Heymann, J., Paschen, S. A., Vier, J., Schauenburg, L., Rupp, J., Meyer, T. F., Häcker, G.* and Heuer, D.* (2011) Targeting of a chlamydial protease impedes intracellular bacterial growth. PLoS Pathogens, 7(9):e1002283.. * Equal contribution.
Volceanov, L., Herbst, K., Biniossek, M., Schilling, O., Haller, D., Nölke, T., Subbarayal, P., Rudel, T., Zieger, B., Häcker, G. (2014) Septins arrange F-actin containing fibers on the Chlamydia trachomatis-inclusion and are required for the normal release of the inclusion by extrusion. MBio, 7;5(5). pii: e01802-1.
Kontchou, C.W., Tzivelekidis, T., Gentle, I.E. and Häcker, G. (2016) Infection of epithelial cells with Chlamydia trachomatis inhibits TNF-induced apoptosis at the level of receptor internalisation while leaving non-apoptotic TNF-signalling intact. Cell Microbiol., Apr 8. doi: 10.1111/cmi.12598.