Department of Microbiology and Immunology, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, USA.
Department of Pathobiology, University of Pennsylvania, School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA.
Microbes Infect. 2014 Jun;16(6):502-11. doi: 10.1016/j.micinf.2014.02.012. Epub 2014 Mar 15.
Neutrophils are multifaceted cells that are often the immune system's first line of defense. Human and murine cells release extracellular DNA traps (ETs) in response to several pathogens and diseases. Neutrophil extracellular trap (NET) formation is crucial to trapping and killing extracellular pathogens. Aside from neutrophils, macrophages and eosinophils also release ETs. We hypothesized that ETs serve as a mechanism of ensnaring the large and highly motile helminth parasite Strongyloides stercoralis thereby providing a static target for the immune response. We demonstrated that S. stercoralis larvae trigger the release of ETs by human neutrophils and macrophages. Analysis of NETs revealed that NETs trapped but did not kill larvae. Induction of NETs was essential for larval killing by human but not murine neutrophils and macrophages in vitro. In mice, extracellular traps were induced following infection with S. stercoralis larvae and were present in the microenvironment of worms being killed in vivo. These findings demonstrate that NETs ensnare the parasite facilitating larval killing by cells of the immune system.
中性粒细胞是一种多功能细胞,通常是免疫系统的第一道防线。人类和鼠类细胞会针对多种病原体和疾病释放细胞外 DNA 陷阱(ETs)。中性粒细胞细胞外陷阱(NET)的形成对于捕获和杀死细胞外病原体至关重要。除了中性粒细胞外,巨噬细胞和嗜酸性粒细胞也会释放 ETs。我们假设 ETs 作为一种捕获大型且高度运动的寄生虫旋毛虫的机制,从而为免疫反应提供一个静态的目标。我们证明旋毛虫幼虫会触发人类中性粒细胞和巨噬细胞释放 ETs。NETs 的分析表明,NETs 捕获但不会杀死幼虫。NETs 的诱导对于人类而非鼠类中性粒细胞和巨噬细胞体外杀死幼虫是必不可少的。在小鼠中,感染旋毛虫幼虫后会诱导细胞外陷阱,并且在体内杀死的蠕虫的微环境中存在细胞外陷阱。这些发现表明,NETs 捕获寄生虫,促进免疫系统细胞杀死幼虫。