Helicobacter pylori-infected human neutrophils exhibit impaired chemotaxis and a uropod retraction defect.
Helicobacter pylori-infected human neutrophils exhibit impaired chemotaxis and a uropod retraction defect.
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DOI：
10.3389/fimmu.2022.1038349
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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幽门螺杆菌（Helicobacter pylori，Hp）是一种主要的人类致病菌，在胃粘膜上定植，在消化性溃疡和胃癌的发生发展中起着重要的作用。中性粒细胞在体内被这种生物体严重感染，并在组织破坏和疾病中发挥重要作用。最近，我们证明了H.幽门螺杆菌利用中性粒细胞可塑性作为其毒力策略的一部分，引起N1样亚型分化，这以深刻的核超分割而闻名。我们进行了这项研究，以测试的假设，超分割可能会提高中性粒细胞的迁移能力。然而，EZ-TAXIScan™视频成像揭示了先前未被认识到的进行性趋化缺陷，其在超分割开始之前是明显的。细胞速度和方向性显著受损fMLF以及C5 a和IL-8。受感染的细胞正常定向在趋化梯度，但速度和方向受损，因为尾足回缩缺陷，导致细胞伸长，核叶陷在收缩后方和渐进缩小的前缘。相反，趋化性受体丰度、粘附、吞噬和细胞功能的其他方面没有变化。在分子水平上，H. pylori的F-actin和actin峰的异常积累以及S19处肌球蛋白IIA调节轻链的增强的ROCKII介导的磷酸化表明了Blebbistatin的作用。同时，RhoA和ROCKII从细胞后部消失并在前缘积累，而肌球蛋白IIA在细胞两极富集。这些数据表明H. pylori抑制肌球蛋白IIA收缩性和前后极性的动态变化，而这对于趋化性是必不可少的。总之，我们的数据推进了对PMN可塑性和H。pylori发病机制
Helicobacter pylori is a major human pathogen that colonizes the gastric mucosa and plays a causative role in development of peptic ulcers and gastric cancer. Neutrophils are heavily infected with this organism in vivo and play a prominent role in tissue destruction and disease. Recently, we demonstrated that H. pylori exploits neutrophil plasticity as part of its virulence strategy eliciting N1-like subtype differentiation that is notable for profound nuclear hypersegmentation. We undertook this study to test the hypothesis that hypersegmentation may enhance neutrophil migratory capacity. However, EZ-TAXIScan™ video imaging revealed a previously unappreciated and progressive chemotaxis defect that was apparent prior to hypersegmentation onset. Cell speed and directionality were significantly impaired to fMLF as well as C5a and IL-8. Infected cells oriented normally in chemotactic gradients, but speed and direction were impaired because of a uropod retraction defect that led to cell elongation, nuclear lobe trapping in the contracted rear and progressive narrowing of the leading edge. In contrast, chemotactic receptor abundance, adhesion, phagocytosis and other aspects of cell function were unchanged. At the molecular level, H. pylori phenocopied the effects of Blebbistatin as indicated by aberrant accumulation of F-actin and actin spikes at the uropod together with enhanced ROCKII-mediated phosphorylation of myosin IIA regulatory light chains at S19. At the same time, RhoA and ROCKII disappeared from the cell rear and accumulated at the leading edge whereas myosin IIA was enriched at both cell poles. These data suggest that H. pylori inhibits the dynamic changes in myosin IIA contractility and front-to-back polarity that are essential for chemotaxis. Taken together, our data advance understanding of PMN plasticity and H. pylori pathogenesis.
DOI：
10.1083/jcb.75.3.666
发表时间：
1977-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Malech HL;Root RK;Gallin JI
通讯作者：
Gallin JI