Surface layer proteins isolated from Clostridium difficile induce clearance responses in macrophages
Surface layer proteins isolated from Clostridium difficile induce clearance responses in macrophages
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DOI：
10.1016/j.micinf.2014.02.001
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发表时间：
2014-05-01
影响因子：
5.8
通讯作者：
Loscher, Christine E.
中科院分区：
文献类型：
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作者：
Collins, Laura E.;Lynch, Mark;Loscher, Christine E.
艰难梭菌是全球医院获得性腹泻的主要原因，如果细菌没有得到有效清除，它可能会造成复发性感染和并发症的风险，如结肠炎，败血症和死亡。在这项研究中，我们证明了来自最常获得的C. difficile，在体外激活鼠巨噬细胞中与细菌感染清除相关的机制。从C.艰难梭菌在体外诱导促炎细胞因子和趋化因子的产生并增加巨噬细胞迁移和吞噬活性。此外，我们还观察到巨噬细胞上的许多细胞表面标志物的上调，这些标志物在病原体识别和抗原呈递中很重要。SLP对巨噬细胞的作用在p38抑制剂的存在下被逆转，表明这种信号蛋白在SLP如何激活免疫系统中的潜在重要性。总之，本研究表明，从一个共同的菌株的C。艰难梭菌能激活巨噬细胞的清除反应，表明这些蛋白在艰难梭菌的清除中是重要的。艰难感染了解免疫系统如何清除C。艰难梭菌感染可以为新的治疗策略提供重要的见解。(C)2014巴斯德研究所。由Elsevier Masson SAS出版。All rights reserved.
Clostridium difficile is the leading cause of hospital-acquired diarrhoea worldwide, and if the bacterium is not cleared effectively it can pose a risk of recurrent infections and complications such as colitis, sepsis and death. In this study we demonstrate that surface layer proteins from the one of the most frequently acquired strains of C. difficile, activate mechanisms in murine macrophage in vitro that are associated with clearance of bacterial infection. Surface layer proteins (SLPs) isolated from C. difficile induced the production of pro-inflammatory cytokines and chemokines and increased macrophage migration and phagocytotic activity in vitro. Furthermore, we also observed up-regulation of a number of cell surface markers on the macrophage, which are important in pathogen recognition and antigen presentation. The effects of SLPs on macrophages were reversed in the presence of a p38 inhibitor, indicating the potential importance of this signalling protein in how SLP activates the immune system. In conclusion this study shows that surface layer proteins from a common strain of C. difficile can activate a clearance response in macrophage and suggests that these proteins are important in clearance of C. difficile infection. Understanding how the immune system clears C. difficile infection could offer important insights for new treatment strategies. (C) 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.