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B01 - Role of apoptotic caspases in macrophage-mediated anti-bacterial immunity

Hamid Kashkar

Institute for Molecular Immunology, CECAD
Contact: h.kashkar(at)uni-koeln.de
For more information visit: Kashkar lab


Macrophages are key players in host defence, inflammation, tissue homeostasis and repair. Different modes of macrophage death including apoptosis, necroptosis and pyroptosis have been described, in particular upon interaction with bacterial pathogens. Recent observations strongly indicated that pro-apoptotic caspase activity is a versatile cellular tool that can cause different cellular outcomes by acting as a switch regulating different modes of cell death. This project will investigate the role of pro-apoptotic caspases in macrophage-mediated anti-bacterial immunity.

Recent Publications


Schorn, F., Werthenbach, J.P., Hoffmann, M., Daoud, M., Stachelscheid, J., Schiffmann, L.M., Hildebrandt, X., Lyu, S.I., Peltzer, N., Quaas, A., Vucic, D., Silke, J., Pasparakis, M. and Kashkar, H. (2023) cIAPs control RIPK1 kinase activity-dependent and -independent cell death and tissue inflammation. EMBO J. doi: 10.15252/embj.2023113614

Injarabian, L., Willenborg, S., Welcker, D., Sanin, D.E., Pasparakis, M., Kashkar, H. and Eming, S.A. (2023) FADD- and RIPK3-mediated cell death ensures clearance of Ly6Chigh wound macrophages from damaged tissue. J Invest Dermatol. doi: 10.1016/j.jid.2023.06.203.


Maekawa, T., Kashkar, H. & Coll, N.S. Dying in self-defence: a comparative overview of immunogenic cell death signalling in animals and plants. Cell Death Differ (2022). https://doi.org/10.1038/s41418-022-01060-6 (review)

Daoud, M., Broxtermann, P.N., Schorn, F., Werthenbach, J.P., Seeger, J.M., Schiffmann, L.M., Brinkmann, K., Vucic, D., Tüting, T., Mauch, C., Kulms, D., Zigrino, P., Kashkar, H. (2022) XIAP promotes melanoma growth by inducing tumour neutrophil infiltration. EMBO Reports (2022)e53608 https://doi.org/10.15252/embr.202153608

Simpson, D.S., Pang, J., Weir, A., Kong, I.Y., Fritsch, M., Rashidi, M., Cooney, J.P., Davidson, K.C., Speir, M., Djajawi, T.M., Hughes, S., Mackiewicz, L., Dayton, M., Anderton, H., Doerflinger, M., Deng, Y., Huang, A.S., Conos, S.A., Tye, H., Chow, S.H.,  Rahman, A., Norton, R.S., Naderer, T., Nicholson, S.E., Burgio, G., Man, S.M., Groom, J.R,. Herold, M.J., Hawkins, E.D., Lawlor, K.E., Strasser, A., Silke, J., Pellegrini, M., Kashkar, H., Feltham, R., Vince, J.E. (2022) Interferon-g primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway. Immunity 55, 1–19, March 8, 2022 https://doi.org/10.1016/j.immuni.2022.01.003


Flores-Romero, H., Hohorst, L., John, M., Albert, M.-C., King, L.E., Beckmann, L., Szabo, T., Hertlein, V., Luo, X., Villunger, A., Frenzel, L.P., Kashkar, H., & Garcia-Saez, A.J. (2021) BCL-2-family protein tBID can act as a BAX-like effector of apoptosis. The EMBO Journal (2021) e108690 DOI10.15252/embj.2021108690

Theobald, S.J., Gräb, J., Fritsch, M., Suárez, I., Eisfeld, H.S., Winter, S., Koch, M., Hölscher, C., Pasparakis, M., Kashkar, H., and Rybniker, J. (2021) Gasdermin D mediates host cell death but not interleukin-1β secretion in Mycobacterium tuberculosis-infected macrophages. Cell Death Discov. 7, 327 (2021). https://doi.org/10.1038/s41420-021-00716-5

Geueke, A., Mantellato, G., Kueste, F., Schettina, P., Nelles, M., Seeger, J.M., Kashkar, H., & Niemann, C. (2021) The anti-apoptotic Bcl-2 protein regulates hair follicle stem cell function. EMBO reports e52301 https://doi.org/10.15252/embr.202052301


Mayer, C.T., Nieke, J.P., Gazumyan, A., Cipolla, M., Wang, Q., Oliveira, Y.T., Ramos, V., Monette, S., Li, Q.Z., Gershwin, M.E., Kashkar, H., Nussenzweig, M.C. (2020) An apoptosis-dependent checkpoint for autoimmunity in memory B and plasma cells. Proc Natl Acad Sci U S A [Epub ahead of print] https://doi.org/10.1073/pnas.2015372117

Albert, M.C., Brinkmann, K., Pokrzywa, W., Günther, S.D., Krönke, M., Hoppe, T. & Kashkar, H. (2020). CHIP ubiquitylates NOXA and induces its lysosomal degradation in response to DNA damage. Cell Death Dis 11, 740. https://doi.org/10.1038/s41419-020-02923-x

Schiffmann, L.M., Werthenbach, J.P., Heintges-Kleinhofer, F., Seeger, J.M., Fritsch, M., Günther, S.D., Willenborg,S., Brodesser,S., Lucas, C. Jüngst, C., Albert, M.C., Schorn, F.,Witt, A., Moraes, C.T., Bruns, C.J., Pasparakis, M., Krönke, M., Eming, S.A., Coutelle, O., Kashkar, H. (2020). Mitochondrial respiration controls neoangiogenesis during wound healing and tumour growth. Nat Comm. Volume 11, Article Number: 3653. https://doi.org/10.1038/s41467-020-17472-2

Günther SD, Fritsch M, Seeger JM, Schiffmann LM, Snipas SJ, Coutelle M, Kufer TA, Higgins PG, Hornung V, Bernardini ML, Höning S, Krönke M, Salvesen GS, Kashkar H. (2020) Cytosolic Gram-negative bacteria prevent apoptosis by inhibition of effector caspases through lipopolysaccharide. Nat. Microbiol. 5:354–367.  

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