Work group Prof. Dr. Andreas Klos
For years, we are investigating Chlamydia and the complement system.
The complement system consists of various proteins, most of them circulating in body fluids and acting as immunological guards or regulators. Receptors for its active components are found on the surface of many host cells, e.g. macrophages. This system plays a central role in the defense against microorganisms. Thereby, it is not only part of the innate immune system, but also strongly influences the development of the specific immune response. However, its over-activation in inflammatory diseases can be deleterious.
Chlamydia are intracellular bacteria. Urogenital infections of women with Chlamydia (C.) trachomatis are frequently asymptomatic and thus, remain often untreated. They can lead to ascending infections of the genital tract with infertility as one important sequela. Infections of pregnant women can harm the newborn. This bacterium is also responsible for trachoma mainly occurring in tropical regions, a chronic-recurring eye illness which can lead to blindness. Even after decades of various attempts, there is still no approved, effective vaccine available. C. psittaci is a zoonotic pathogen. After its transmission from birds, life-threatening pneumonia occurs in man. Moreover, this chlamydial species is of economic importance in livestock. C. pneumoniae is a frequent cause of usually mild respiratory infections. Additionally, it is discussed in the context of vascular inflammatory diseases.
One of our research projects focuses on the development and characterization of a protective vaccine against C. trachomatis, in particular to prevent the feared sequelae of an infection. In another project we elucidate the role of the complement system in the defense against C. psittaci. Here, we are particularly interested in the function of complement factor C3 and its cleavage product C3a with the corresponding receptor in the development of a specific T cell response. In a third project we characterize pathogenicity factors of C. trachomatis and their orthologs in C. psittaci and further, zoonotic chlamydial species. Thereby we put our focus on bacterial proteins which are transferred into the host cell and modify its biochemical-functional behavior.
We are grateful for financial support by the German Research Foundation (DFG KL-603/10-1).
Most important publications:
- Rother M, Gonzalez E, Teixeira da Costa AR, Wask L, Gravenstein I, Pardo M, Pietzke M, Gurumurthy RK, Angermann A, Laudeley R, Glage S. Meyer M., Chumduri C, Kempa S, Dinkel K, Unger A, Kleb B, Klos A, Meyer TF. 2018 Combined human genome-wide RNAi and metabolite analyses identify IMPDH as a host-directed target against Chlamydia infection, Cell Host Microbe. 23:661-671.
- Arbore G, West EE, Spolski R, Robertson AAB, Klos A, Rheinheimer C, Dutow D, Woodruff T, Yu ZX, O'Neill LA, Coll RC, Sher A, Leonard WJ, Köhl J, Monk P, Cooper MA, Arno M, Afzali B, Lachmann HJ, Cope AP, Mayer-Barber KD, Claudia Kemper. 2016. T helper 1 immunity requires complement-driven, NLRP3 inflammasome activity in CD4+ T cells. Science. 352:aad1210.
- Dutow P, Fehlhaber B, Bode J, Laudeley R, Rheinheimer C, Glage S, Wetsel RA, Pabst O, Klos A. 2014. The complement C3a receptor is critical in defense against Chlamydia psittaci in mouse lung infection and required for antibody and optimal T cell response. J. Infect. Dis. 8:3366-74.
- Schatz-Jakobsen JA, Yatime L, Larsen C, Petersen SV, Klos A, Andersen GR. 2014. Structural and functional characterization of human and murine C5a anaphylatoxins. Acta Crystallogr. D Biol. Crystallogr. 70:1704-1717.
- Thalman J, Janik K., May M, Sommer K, Ebeling J, Hofmann F, Genth H, Klos A. 2010. Actin re-organization induced by Chlamydia trachomatis Serovar D - Evidence for a critical role of the effector protein CT166 targeting Rac. PLoS ONE. 5(3):e9887.
- Johswich K, Martin M, Bleich A, Kracht M, Dittrich-Breiholz O, Gessner JE, Suerbaum S, Wende E. Rheinheimer C, Klos A. 2009. Role of the C5a receptor (C5aR) in acute and chronic dextran sulfate-induced models of inflammatory bowel disease. Inflamm. Bowel Dis. 15(12):1812-1823.
- Johswich K, Martin M, Thalmann J, Rheinheimer C, Monk PN, Klos A. 2006. Ligand specificity of the anaphylatoxin C5L2 receptor and its regulation on myeloid and epithelial cell-lines. J. Biol. Chem. 281:39088-39095.
- Peters J, Hess S., Endlich K, Thalmann J, Holzberg D, Kracht M, Schaefer M, Bartling G, Klos A. 2005. Silencing and permanent activation: Host-cell responses in models of persistent Chlamydia pneumoniae infection. Cell. Microbiol. 7: 1099-1108.
- Fischer S F, Vier J J, Kirschnek S, Klos A, Hess S, Häcker G. 2004. Chlamydia inhibit host cell-apoptosis by specific degradation of the pro-apoptotic BH3-only protein Bim. J. Exp. Med. 200:905-916.
- Martin U, Bock D, Arseniev L, Tornetta M A, Ames R S, Bautsch W, Köhl J, Ganser A, Klos A. 1997. The human C3a receptor is expressed on neutrophils and monocytes, but not on B or T lymphocytes. J. Exp. Med. 186:199-207.