TY - JOUR A1 - Rajalingam, Krishnaraj A1 - Sharma, Manu A1 - Lohmann, Christine A1 - Oswald, Monique A1 - Thieck, Oliver A1 - Froelich, Christopher J. A1 - Rudel, Thomas T1 - Mcl-1 is a key regulator of apoptosis resistance in Chlamydia trachomatis-infected cells T2 - PLoS One N2 - Chlamydia are obligate intracellular bacteria that cause variety of human diseases. Host cells infected with Chlamydia are protected against many different apoptotic stimuli. The induction of apoptosis resistance is thought to be an important immune escape mechanism allowing Chlamydia to replicate inside the host cell. Infection with C. trachomatis activates the Raf/MEK/ERK pathway and the PI3K/AKT pathway. Here we show that inhibition of these two pathways by chemical inhibitors sensitized C. trachomatis infected cells to granzyme B-mediated cell death. Infection leads to the Raf/MEK/ERK-mediated up-regulation and PI3K-dependent stabilization of the anti-apoptotic Bcl-2 family member Mcl-1. Consistently, interfering with Mcl-1 up-regulation sensitized infected cells for apoptosis induced via the TNF receptor, DNA damage, granzyme B and stress. Our data suggest that Mcl-1 up-regulation is primarily required to maintain apoptosis resistance in C. trachomatis-infected cells. Y1 - 2008 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22620 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30-114654 SN - 1932-6203 N1 - Copyright: © 2008 Rajalingam et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. VL - 3 IS - (9): e3102 ER -