Cell-Cell Propagation of NF-κB Transcription Factor and MAP Kinase Activation Amplifies Innate Immunity against Bacterial Infection
Cell-Cell Propagation of NF-κB Transcription Factor and MAP Kinase Activation Amplifies Innate Immunity against Bacterial Infection
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DOI：
10.1016/j.immuni.2010.10.015
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发表时间：
2010-11-24
期刊：
影响因子：
32.4
通讯作者：
Arrieumerlou, Cecile
中科院分区：
文献类型：
--
作者：
Kasper, Christoph Alexander;Sorg, Isabel;Arrieumerlou, Cecile
肠道侵袭性细菌福氏志贺氏菌利用多种分泌的效应蛋白来下调受感染的上皮细胞中白介素8(IL-8)的表达。然而，在志贺氏菌病中观察到大量的IL-8分泌。在这里，我们报告了在细菌感染过程中绕过效应蛋白并强烈增强IL-8表达的细胞-细胞通讯的宿主机制。通过在单细胞水平监测促炎信号，我们发现转录因子NF-kappa B和MAP激酶JNK、ERK和p38的激活从感染的邻近细胞迅速传播到未感染的邻近细胞，导致未感染的旁观者细胞产生IL-8。在单核细胞增多性李斯特菌和鼠伤寒沙门氏菌感染过程中也观察到旁观者IL-8的产生。这种反应可能由识别肽聚糖而触发，并由缝隙连接介导。因此，我们已经确定了一种细胞-细胞交流的机制，通过缝隙连接将促炎信号快速传播到尚未感染的细胞，从而增强对细菌感染的先天免疫。
The enteroinvasive bacterium Shigella flexneri uses multiple secreted effector proteins to downregulate interleukin-8 (IL-8) expression in infected epithelial cells. Yet, massive IL-8 secretion is observed in Shigellosis. Here we report a host mechanism of cell-cell communication that circumvents the effector proteins and strongly amplifies IL-8 expression during bacterial infection. By monitoring proinflammatory signals at the single-cell level, we found that the activation of the transcription factor NF-kappa B and the MAP kinases JNK, ERK, and p38 rapidly propagated from infected to uninfected adjacent cells, leading to IL-8 production by uninfected bystander cells. Bystander IL-8 production was also observed during Listeria monocyto genes and Salmonella typhimurium infection. This response could be triggered by recognition of peptidoglycan and is mediated by gap junctions. Thus, we have identified a mechanism of cell-cell communication that amplifies innate immunity against bacterial infection by rapidly spreading proinflammatory signals via gap junctions to yet uninfected cells.