Campylobacter jejuni is the leading cause of bacterial‐derived gastroenteritis worldwide and can lead to several post‐infectious inflammatory disorders. Despite the prevalence and health impacts of the bacterium, interactions between the host innate immune system and C. jejuni remain poorly understood. To expand on earlier work demonstrating that neutrophils traffic to the site of infection in an animal model of campylobacteriosis, we identified significant increases in several predominantly neutrophil‐derived proteins in the faeces of C. jejuni‐ infected patients, including lipocalin‐2, myeloperoxidase and neutrophil elastase. In addition to demonstrating that these proteins significantly inhibited C. jejuni growth, we determined they are released during formation of C. jejuni‐ induced neutrophil extracellular traps (NETs). Using quantitative and qualitative methods, we found that purified human neutrophils are activated by C. jejuni and exhibit signatures of NET generation, including presence of protein arginine deiminase‐4, histone citrullination, myeloperoxidase, neutrophil elastase release and DNA extrusion. Production of NETs correlated with C. jejuni phagocytosis/endocytosis and invasion of neutrophils suggesting that host‐ and bacterial‐mediated activities are responsible for NET induction. Further, NET‐like structures were observed within intestinal tissue of C. jejuni ‐infected ferrets. Finally, induction of NETs significantly increased human colonocyte cytotoxicity, indicating that NET formation during C. jejuni infection may contribute to observed tissue pathology. These findings provide further understanding of C. jejuni –neutrophil interactions and inflammatory responses during campylobacteriosis.

中文翻译：

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空肠弯曲杆菌诱导中性粒细胞胞外陷阱。


空肠弯曲菌是全世界细菌源性胃肠炎的主要原因，可导致多种感染后炎症性疾病。尽管这种细菌的流行和健康影响，但宿主先天免疫系统和空肠弯曲菌之间的相互作用仍然知之甚少。为了扩展早期证明中性粒细胞在弯曲菌病动物模型中运输至感染部位的工作，我们发现空肠弯曲菌感染患者的粪便中几种主要源自中性粒细胞的蛋白质显着增加，包括脂质运载蛋白-2、髓过氧化物酶和中性粒细胞弹性蛋白酶。除了证明这些蛋白质显着抑制空肠弯曲菌生长之外，我们还确定它们在空肠弯曲菌诱导的中性粒细胞胞外陷阱（NET）形成过程中释放。使用定量和定性方法，我们发现纯化的人中性粒细胞被空肠弯曲菌激活，并表现出 NET 生成的特征，包括蛋白质精氨酸脱亚胺酶 4、组蛋白瓜氨酸化、髓过氧化物酶、中性粒细胞弹性蛋白酶释放和 DNA 挤出的存在。 NET 的产生与空肠弯曲菌吞噬/内吞作用和中性粒细胞的侵袭相关，表明宿主和细菌介导的活动是 NET 诱导的原因。此外，在空肠弯曲菌感染的雪貂的肠道组织内观察到了 NET 样结构。最后，NET 的诱导显着增加了人类结肠细胞的细胞毒性，表明空肠弯曲菌感染期间 NET 的形成可能有助于观察到的组织病理学。这些发现加深了人们对C.的理解。 弯曲菌病期间空肠-中性粒细胞相互作用和炎症反应。