Uropathogenic Escherichia coli triggers oxygen-dependent apoptosis in human neutrophils through the cooperative effect of type 1 fimbriae and lipopolysaccharide
Uropathogenic Escherichia coli triggers oxygen-dependent apoptosis in human neutrophils through the cooperative effect of type 1 fimbriae and lipopolysaccharide
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DOI：
10.1128/iai.72.8.4570-4578.2004
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发表时间：
2004-08-01
影响因子：
3.1
通讯作者：
Stendahl, O
中科院分区：
文献类型：
--
作者：
Blomgran, R;Zheng, LM;Stendahl, O
1 型菌毛是尿路致病性大肠杆菌最常表达的毒力因子。除了促进细菌粘附在尿路上皮上并实现定植之外，1 型菌毛还会将中性粒细胞募集到泌尿道作为早期炎症反应。使用 1 型菌毛大肠杆菌的临床分离株和缺乏 FimH 粘附素的同基因 1 型菌毛阴性突变体 (CN1016)，我们研究了这些菌株是否可以调节人中性粒细胞的凋亡。我们发现表达 1 型菌毛的大肠杆菌以甘露糖和脂多糖 (LPS) 依赖性方式与中性粒细胞相互作用，导致细胞内活性氧的产生引发细胞凋亡。通过阻断 FimH 介导的附着、抑制 NADPH 氧化酶激活或中和 LPS，可以消除这种诱导的中性粒细胞凋亡。相比之下，CN1016不粘附或激活中性粒细胞的呼吸爆发，以LPS依赖性方式延迟自发性细胞凋亡。这种延迟的细胞凋亡可以通过添加纯化的 LPS 来模拟，并且也可以通过在 D-甘露糖存在下使用流苏细菌来观察。这些结果表明 LPS 是大肠杆菌对中性粒细胞发挥促凋亡和抗凋亡作用所必需的，并且 LPS 呈现的差异（即有或没有菌毛）决定了结果。本研究表明，1 型菌毛诱导的和 LPS 介导的人类中性粒细胞凋亡延迟之间存在微调平衡，其中尿路致病性大肠杆菌菌毛表达的改变决定了中性粒细胞的存活以及尿路感染期间随后的炎症。
Type 1 fimbriae are the most commonly expressed virulence factor on uropathogenic Escherichia coli. In addition to promoting avid bacterial adherence to the uroepithelium and enabling colonization, type 1 fimbriae recruit neutrophils to the urinary tract as an early inflammatory response. Using clinical isolates of type 1 fimbriated E. coli and an isogenic type 1 fimbria-negative mutant (CN1016) lacking the FimH adhesin, we investigated if these strains could modulate apoptosis in human neutrophils. We found that E. coli expressing type 1 fimbriae interacted with neutrophils in a mannose- and lipopolysaccharide (LPS)-dependent manner, leading to apoptosis which was triggered by the intracellular generation of reactive oxygen species. This induced neutrophil apoptosis was abolished by blocking FimH-mediated attachment, by inhibiting NADPH oxidase activation, or by neutralizing LPS. In contrast, CN1016, which did not adhere to or activate the respiratory burst of neutrophils, delayed the spontaneous apoptosis in an LPS-dependent manner. This delayed apoptosis could be mimicked by adding purified LPS and was also observed by using fimbriated bacteria in the presence of D-mannose. These results suggest that LPS is required for E. coli to exert both pro- and antiapoptotic effects on neutrophils and that the difference in LPS presentation (i.e., with or without fimbriae) determines the outcome. The present study showed that there is a fine-tuned balance between type 1 fimbria-induced and LPS-mediated delay of apoptosis in human neutrophils, in which altered fimbrial expression on uropathogenic E. coli determines the neutrophil survival and the subsequent inflammation during urinary tract infections.