Apoptosis of human intestinal epithelial cells after bacterial invasion
Apoptosis of human intestinal epithelial cells after bacterial invasion
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DOI：
10.1172/jci2466
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发表时间：
1998-11-15
影响因子：
15.9
通讯作者：
Kagnoff, MF
中科院分区：
文献类型：
--
作者：
Kim, JM;Eckmann, L;Kagnoff, MF
人类肠粘膜上皮细胞是细菌病原体入侵宿主的初始部位。本文的研究将细胞凋亡定义为肠上皮细胞对细菌感染的一种新的反应。研究表明，人结肠上皮细胞在感染沙门氏菌或肠侵袭性大肠杆菌等侵入性肠道病原体后会发生凋亡。与小鼠单核-巨噬细胞系细菌感染后细胞凋亡的快速发生相反，人肠上皮细胞系在细菌感染后经历细胞凋亡的承诺延迟至少6小时，需要细菌进入和复制，并且随后的细胞凋亡表型表达在细菌进入后延迟12-18小时。 TNF-α和一氧化氮作为细菌入侵后早期肠上皮细胞促炎程序的组成部分产生，在后期诱导和调节上皮细胞凋亡程序中发挥重要作用。细菌感染引起的细胞凋亡可能会消除受感染和受损的上皮细胞，恢复肠道感染过程中改变的上皮细胞生长调节和上皮完整性。细菌感染后上皮细胞凋亡的延迟对于宿主和入侵的病原体来说可能都很重要，因为它为上皮细胞提供了足够的时间来产生对激活粘膜炎症很重要的信号，同时允许入侵细菌在侵入更深的粘膜层之前有时间适应细胞内环境。
Epithelial cells that line the human intestinal mucosa are the initial site of host invasion by bacterial pathogens. The studies herein define apoptosis as a new category of intestinal epithelial cell response to bacterial infection. Human colon epithelial cells are shown to undergo apoptosis following infection with invasive enteric pathogens, such as Salmonella or enteroinvasive Escherichia coli. In contrast to the rapid onset of apoptosis seen after bacterial infection of mouse monocyte-macrophage cell lines, the commitment of human intestinal epithelial cell lines to undergo apoptosis is delayed for at least 6 h after bacterial infection, requires bacterial entry and replication, and the ensuing phenotypic expression of apoptosis is delayed for 12-18 h after bacterial entry. TNF-alpha and nitric oxide, which are produced as components of the intestinal epithelial cell proinflammatory program in the early period after bacterial invasion, play an important role in the later induction and regulation of the epithelial cell apoptotic program. Apoptosis in response to bacterial infection may function to delete infected and damaged epithelial cells and restore epithelial cell growth regulation and epithelial integrity that are altered during the course of enteric infection. The delay in onset of epithelial cell apoptosis after bacterial infection may be important both to the host and the invading pathogen since it provides sufficient time for epithelial cells to generate signals important for the activation of mucosal inflammation and concurrently allows invading bacteria time to adapt to the intracellular environment before invading deeper mucosal layers.