美国和瑞士科学家近日研究揭示了嗜曙红细胞(eosinophil,白细胞的一种)帮助机体抵御细菌感染的机制。研究发现,嗜曙红细胞能被细菌激活,用类似“弹弓”的方式释放出线粒体DNA,创建成一张“网”捕获并杀死细菌。相关论文发表在《自然—医学》(Nature Medicine)上。
嗜曙红细胞仅占人体白细胞组成的1%-3%。此前,科学家已经知道它们有助于人体防御寄生虫,但对于其在免疫系统中的具体角色并不清楚。与其它种白细胞遍布全身不同,嗜曙红细胞只发现于消化道等特定区域。
之前的研究发现,在细菌感染时,嗜曙红细胞会分泌有毒颗粒蛋白,这些颗粒蛋白会杀死细菌。在最新的研究中,瑞士伯尔尼大学的Hans-Uwe Simon和美国犹他大学的Gerald J.Gleich及同事发现,当嗜曙红细胞受到细菌感染的刺激时,它们会如弹弓发射一般,快速分泌出线粒体DNA。线粒体DNA会绑定在颗粒蛋白上,形成一张能够捕获并杀死细菌的网。
不过,嗜曙红细胞释放的有毒蛋白并不总是对机体有益,它也会损伤附近的组织。比如某些种类的哮喘和克罗恩氏病就要归因于嗜曙红细胞。
研究人员希望能更多地了解嗜曙红细胞“发射”线粒体DNA的机制,他们推测,这种机制可能依赖于储存的能量,与植物释放花粉的方式类似。Gleich说:“这是一个吸引人的发现,线粒体DNA被发射出细胞的时间要短于1秒,但我们并不清楚嗜曙红细胞怎样能够如此快速地弹射出线粒体DNA。”(生物谷Bioon.com)
生物谷推荐原始出处:
Nature Medicine,doi:10.1038/nm.1855,Shida Yousefi,Hans-Uwe Simon
Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense
Shida Yousefi1, Jeffrey A Gold2, Nicola Andina1, James J Lee3, Ann M Kelly2, Evelyne Kozlowski1, Inès Schmid1, Alex Straumann4, Janine Reichenbach5, Gerald J Gleich6 & Hans-Uwe Simon1
Although eosinophils are considered useful in defense mechanisms against parasites, their exact function in innate immunity remains unclear. The aim of this study is to better understand the role of eosinophils within the gastrointestinal immune system. We show here that lipopolysaccharide from Gram-negative bacteria activates interleukin-5 (IL-5)- or interferon-–primed eosinophils to release mitochondrial DNA in a reactive oxygen species–dependent manner, but independent of eosinophil death. Notably, the process of DNA release occurs rapidly in a catapult-like manner—in less than one second. In the extracellular space, the mitochondrial DNA and the granule proteins form extracellular structures able to bind and kill bacteria both in vitro and under inflammatory conditions in vivo. Moreover, after cecal ligation and puncture, Il5-transgenic but not wild-type mice show intestinal eosinophil infiltration and extracellular DNA deposition in association with protection against microbial sepsis. These data suggest a previously undescribed mechanism of eosinophil-mediated innate immune responses that might be crucial for maintaining the intestinal barrier function after inflammation-associated epithelial cell damage, preventing the host from uncontrolled invasion of bacteria.