Shigella impairs T lymphocyte dynamics in vivo
Shigella impairs T lymphocyte dynamics in vivo
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DOI：
10.1073/pnas.1300981110
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发表时间：
2013-03-19
影响因子：
11.1
通讯作者：
Phalipon, Armelle
中科院分区：
文献类型：
--
作者：
Salgado-Pabon, Wilmara;Celli, Susanna;Phalipon, Armelle
革兰氏阴性肠侵入性细菌福氏志贺氏菌是地方性的细菌性痢疾的罪魁祸首，这是人类的一种急性直肠结肠炎。flexneri使用III型分泌系统将效应蛋白注入宿主细胞，从而将细胞功能转移到自己的利益上。对再感染的保护性免疫需要几轮感染才能引起，而且持续时间短，这表明弗氏沙门氏菌干扰了特异性免疫的启动。考虑到t淋巴细胞运输在启动适应性免疫中的关键作用，我们研究了flexneri对体内t细胞动力学的影响。通过使用双光子显微镜观察淋巴结中细菌-T细胞的交叉对话，我们提供的证据表明，flexneri通过其III型分泌系统，损害CD4(+) T细胞的迁移模式，而不依赖于对细菌抗原的同源识别。我们发现细菌入侵CD4(+) T淋巴细胞发生在体内，并导致细胞迁移停滞。在没有侵袭的情况下，CD4(+) t细胞的迁移参数也会发生显著改变。flexners与囊下窦巨噬细胞和树突状细胞相互作用产生的信号，以及多形核细胞的募集可能是导致这一现象的原因。这些发现表明flexneri在体内靶向T淋巴细胞，并突出了III型效应物分泌在调节宿主适应性免疫反应中的作用。
The Gram-negative enteroinvasive bacterium Shigella flexneri is responsible for the endemic form of bacillary dysentery, an acute rectocolitis in humans. S. flexneri uses a type III secretion system to inject effector proteins into host cells, thus diverting cellular functions to its own benefit. Protective immunity to reinfection requires several rounds of infection to be elicited and is short-lasting, suggesting that S. flexneri interferes with the priming of specific immunity. Considering the key role played by T-lymphocyte trafficking in priming of adaptive immunity, we investigated the impact of S. flexneri on T-cell dynamics in vivo. By using two-photon microscopy to visualize bacterium-T-cell cross-talks in the lymph nodes, where the adaptive immunity is initiated, we provide evidence that S. flexneri, via its type III secretion system, impairs the migration pattern of CD4(+) T cells independently of cognate recognition of bacterial antigens. We show that bacterial invasion of CD4(+) T lymphocytes occurs in vivo, and results in cell migration arrest. In the absence of invasion, CD4(+) T-cell migration parameters are also dramatically altered. Signals resulting from S. flexneri interactions with subcapsular sinus macrophages and dendritic cells, and recruitment of polymorphonuclear cells are likely to contribute to this phenomenon. These findings indicate that S. flexneri targets T lymphocytes in vivo and highlight the role of type III effector secretion in modulating host adaptive immune responses.