Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH-4056, Basel, Switzerland.
Immunity. 2010 Nov 24;33(5):804-16. doi: 10.1016/j.immuni.2010.10.015.
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-κB 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 monocytogenes 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.
侵袭性肠道细菌福氏志贺菌利用多种分泌效应蛋白下调感染上皮细胞中白细胞介素-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，我们报告了一种宿主细胞间通讯机制，该机制绕过效应蛋白，并在细菌感染期间强烈放大 IL-8 的表达。通过在单细胞水平监测促炎信号，我们发现转录因子 NF-κB 和 MAP 激酶 JNK、ERK 和 p38 的激活迅速从受感染的相邻细胞传播到未受感染的相邻细胞，导致未受感染的旁观者细胞产生 IL-8。在单核细胞增生李斯特菌和鼠伤寒沙门氏菌感染期间也观察到旁观者 IL-8 的产生。这种反应可以通过识别肽聚糖而触发，并且由间隙连接介导。因此，我们已经确定了一种细胞间通讯机制，该机制通过间隙连接快速传播促炎信号来放大针对细菌感染的先天免疫，从而将信号传递到尚未感染的细胞。
