Streptococcus pyogenes induces oncosis in macrophages through the activation of an inflammatory programmed cell death pathway
Streptococcus pyogenes induces oncosis in macrophages through the activation of an inflammatory programmed cell death pathway
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DOI：
10.1111/j.1462-5822.2008.01245.x
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发表时间：
2009-01-01
影响因子：
3.4
通讯作者：
Medina, Eva
中科院分区：
文献类型：
--
作者：
Goldmann, Oliver;Sastalla, Inka;Medina, Eva
巨噬细胞是宿主防御化脓性链球菌的重要组成部分。在这里，我们证明了化脓性葡萄球菌通过激活炎症程序性细胞死亡途径杀死巨噬细胞的能力。暴露于化脓性葡萄球菌的巨噬细胞表现出广泛的细胞质空泡化，细胞和细胞器肿胀以及肿瘤典型的质膜破裂。化脓性链球菌对巨噬细胞的细胞毒作用是由链球菌溶细胞素S和O介导的，不需要细菌内化。添加渗透保护剂不影响化脓链球菌诱导的巨噬细胞死亡，提示激活了一个精心安排的细胞死亡途径，而不是简单的渗透裂解。这种程序性细胞死亡途径涉及线粒体跨膜电位（δ psi(m)）的丧失，并被外源性甘氨酸的添加所抑制，已被证明通过阻断质膜中死亡通道的打开来防止坏死细胞死亡。活性氧的产生和钙蛋白酶的活化被认为是细胞死亡过程的介质。我们得出结论，巨噬细胞炎症性程序性细胞死亡途径的激活可能是化脓性葡萄球菌逃避宿主免疫防御而导致疾病的重要致病机制。
Macrophages are crucial components of the host defence against Streptococcus pyogenes. Here, we demonstrate the ability of S. pyogenes to kill macrophages through the activation of an inflammatory programmed cell death pathway. Macrophages exposed to S. pyogenes exhibited extensive cytoplasmic vacuolization, cellular and organelle swelling and rupture of the plasma membrane typical of oncosis. The cytotoxic effect of S. pyogenes on macrophages is mediated by the streptococcal cytolysins streptolysin S and streptolysin O and does not require bacterial internalization. S. pyogenes-induced death of macrophages was not affected by the addition of osmoprotectant, implicating the activation of an orchestrated cell death pathway rather than a simple osmotic lysis. This programme cell death pathway involves the loss of mitochondria transmembrane potential (Delta psi(m)) and was inhibited by the addition of exogenous glycine, which has been shown to prevent necrotic cell death by blocking the opening of death channels in the plasma membrane. The production of reactive oxygen species and activation of calpains were identified as mediators of the cell death process. We conclude that activation of the inflammatory programmed cell death pathway in macrophages could constitute an important pathogenic mechanism by which S. pyogenes evades host immune defences and causes disease.