Schumacher Pia Philippa, Ajendra Jesuthas, Lenz Benjamin, Risch Frederic, Ehrens Alexandra, Nieto-Pérez Celia, Koschel Marianne, Aden Tilman, Hoerauf Achim, Hübner Marc P
Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.
PLoS Negl Trop Dis. 2025 Mar 3;19(3):e0012889. doi: 10.1371/journal.pntd.0012889. eCollection 2025 Mar.
Eosinophils are a hallmark of filarial infections. They are primary effector cells and can attack filariae by releasing extracellular traps that contain toxic cationic proteins, such as eosinophil peroxidase and major basic protein. Previous studies demonstrated that the extracellular traps of eosinophils are induced by the microfilariae of Litomosoides sigmodontis and that they inhibit their motility. In this project, we aimed to investigate the role of these cationic proteins during the extracellular trap-mediated immobilization of microfilariae. Our results indicate that extracellular DNA traps from knockout mice that lack eosinophil peroxidase or major basic protein are significantly less able to immobilize and kill microfilariae. Accordingly, the addition of these cationic proteins to in vitro cultures inhibited microfilariae motility in a dose-dependent manner. Moreover, we examined eosinophils from the natural host, the cotton rat Sigmodon hispidus. While eosinophils of cotton rats release DNA after stimulation with PMA and zymosan, microfilariae did not trigger this effector function. Our work shows that eosinophil granule proteins impair the motility of microfilariae and indicate significant differences in the effector functions of eosinophils between the mouse model and the natural host. We hypothesize that the absence of DNA nets released by cotton rat eosinophils in response to microfilariae may explain the higher microfilarial load and longer patency of the natural host.
嗜酸性粒细胞是丝虫感染的一个标志。它们是主要的效应细胞，可通过释放含有毒性阳离子蛋白（如嗜酸性粒细胞过氧化物酶和主要碱性蛋白）的细胞外陷阱来攻击丝虫。先前的研究表明，嗜酸性粒细胞的细胞外陷阱是由巴西日圆线虫的微丝蚴诱导产生的，并且它们会抑制微丝蚴的运动。在本项目中，我们旨在研究这些阳离子蛋白在细胞外陷阱介导的微丝蚴固定过程中的作用。我们的结果表明，来自缺乏嗜酸性粒细胞过氧化物酶或主要碱性蛋白的基因敲除小鼠的细胞外DNA陷阱固定和杀死微丝蚴的能力明显较弱。因此，将这些阳离子蛋白添加到体外培养物中会以剂量依赖的方式抑制微丝蚴的运动。此外，我们检查了天然宿主棉鼠（Sigmodon hispidus）的嗜酸性粒细胞。虽然棉鼠的嗜酸性粒细胞在用佛波酯（PMA）和酵母聚糖刺激后会释放DNA，但微丝蚴不会触发这种效应功能。我们的研究表明，嗜酸性粒细胞颗粒蛋白会损害微丝蚴的运动，并表明小鼠模型和天然宿主的嗜酸性粒细胞效应功能存在显著差异。我们推测，棉鼠嗜酸性粒细胞对微丝蚴无反应而不释放DNA网可能解释了天然宿主中较高的微丝蚴负荷和较长的感染期。
