Sarkar Arup, Möller Sonja, Bhattacharyya Asima, Behnen Martina, Rupp Jan, van Zandbergen Ger, Solbach Werner, Laskay Tamás
Institute for Medical Microbiology and Hygiene, University of Lübeck, German Center for Infection Research (DZIF), Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Institute for Medical Microbiology and Hygiene, University of Lübeck, German Center for Infection Research (DZIF), Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Int J Med Microbiol. 2015 Sep;305(6):493-500. doi: 10.1016/j.ijmm.2015.04.006. Epub 2015 May 8.
The obligatory intracellular bacterium Chlamydia pneumoniae (C. pneumoniae) can survive and multiply in neutrophil granulocytes. Since neutrophils are short living cells, inhibition of neutrophil apoptosis appears to play a major role in the productive infection of neutrophils by C. pneumoniae. In the present study, we have investigated which survival pathways and which events of the apoptotic process are modulated in C. pneumoniae-infected neutrophils. All infection experiments were carried out using primary human neutrophils in vitro. We show that infection with C. pneumoniae activates PI3K/Akt as well as the ERK1/2 and p38 MAP kinases and present evidence that activation of the PI3K/Akt and ERK1/2 pathways are essential to initiate the apoptosis delay in C. pneumoniae-infected neutrophils. Both the PI3K/Akt and ERK1/2 pathways are involved in the maintained expression of the anti-apoptotic protein Mcl-1. In addition, we also showed that the PI3K/Akt pathway leads to the activation of NF-κB-dependent release of IL-8 by infected neutrophils. Infection with C. pneumoniae activates the PI3K/Akt and ERK1/2 MAPK survival pathways in neutrophils, induces the NF-κB dependent release of IL-8 and leads to the maintenance of Mcl-1 expression in neutrophils.
专性胞内细菌肺炎衣原体（C. pneumoniae）可在中性粒细胞中存活并繁殖。由于中性粒细胞是寿命较短的细胞，抑制中性粒细胞凋亡似乎在肺炎衣原体对中性粒细胞的有效感染中起主要作用。在本研究中，我们调查了肺炎衣原体感染的中性粒细胞中哪些生存途径以及凋亡过程的哪些事件受到调节。所有感染实验均使用原代人中性粒细胞在体外进行。我们发现，肺炎衣原体感染可激活PI3K/Akt以及ERK1/2和p38丝裂原活化蛋白激酶，并提供证据表明PI3K/Akt和ERK1/2途径的激活对于引发肺炎衣原体感染的中性粒细胞凋亡延迟至关重要。PI3K/Akt和ERK1/2途径均参与抗凋亡蛋白Mcl-1的持续表达。此外，我们还表明PI3K/Akt途径导致感染的中性粒细胞激活NF-κB依赖的IL-8释放。肺炎衣原体感染可激活中性粒细胞中的PI3K/Akt和ERK1/2丝裂原活化蛋白激酶生存途径，诱导NF-κB依赖的IL-8释放，并导致中性粒细胞中Mcl-1表达的维持。
