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首页> 外文期刊>Infection and immunity >Afa/Dr Diffusely Adhering Escherichia coli Strain C1845 Induces Neutrophil Extracellular Traps That Kill Bacteria and Damage Human Enterocyte-Like Cells
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Afa/Dr Diffusely Adhering Escherichia coli Strain C1845 Induces Neutrophil Extracellular Traps That Kill Bacteria and Damage Human Enterocyte-Like Cells

机译：Afa / Dr弥漫性粘附大肠杆菌菌株C1845诱导嗜中性粒细胞胞外陷阱杀死细菌并破坏人类肠上皮细胞样细胞

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We recently documented the neutrophil response to enterovirulent diffusely adherent Escherichia coli expressing Afa/Dr fimbriae (Afa/Dr DAEC), using the human myeloid cell line PLB-985 differentiated into fully mature neutrophils. Upon activation, particularly during infections, neutrophils release neutrophil extracellular traps (NETs), composed of a nuclear DNA backbone associated with antimicrobial peptides, histones, and proteases, which entrap and kill pathogens. Here, using fluorescence microscopy and field emission scanning electron microscopy, we observed NET production by PLB-985 cells infected with the Afa/Dr wild-type (WT) E. coli strain C1845. We found that these NETs were able to capture, immobilize, and kill WT C1845 bacteria. We also developed a coculture model of human enterocyte-like Caco-2/TC7 cells and PLB-985 cells previously treated with WT C1845 and found, for the first time, that the F-actin cytoskeleton of enterocyte-like cells is damaged in the presence of bacterium-induced NETs and that this deleterious effect is prevented by inhibition of protease release. These findings provide new insights into the neutrophil response to bacterial infection via the production of bactericidal NETs and suggest that NETs may damage the intestinal epithelium, particularly in situations such as inflammatory bowel diseases.
机译：我们最近使用分化为完全成熟的嗜中性粒细胞的人类骨髓细胞系PLB-985，记录了对表达Afa / Dr菌毛（Afa / Dr DAEC）的肠毒力弥漫性粘附大肠杆菌的嗜中性粒细胞反应。活化后，特别是在感染过程中，中性粒细胞释放中性粒细胞胞外陷阱（NETs），该陷阱由与抗菌肽，组蛋白和蛋白酶相关的核DNA骨架构成，从而捕获并杀死病原体。在这里，使用荧光显微镜和场发射扫描电子显微镜，我们观察到被Afa / Dr野生型（WT）大肠杆菌C1845感染的PLB-985细胞的NET产生。我们发现这些NET能够捕获，固定和杀死WT C1845细菌。我们还开发了人类肠道细胞样Caco-2 / TC7细胞和先前用WT C1845处理过的PLB-985细胞的共培养模型，并首次发现肠样细胞中F-肌动蛋白细胞骨架被破坏。细菌诱导的NETs的存在，并通过抑制蛋白酶的释放来防止这种有害作用。这些发现为中性粒细胞通过产生杀菌性网产生了对细菌感染的反应提供了新的见解，并暗示了网可能损害肠上皮，尤其是在炎症性肠病等情况下。

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