Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn 53127, Germany.
UMR7245 MCAM Museum National d'Histoire Naturelle, CNRS, Paris, France.
Cell Rep. 2021 Jan 12;34(2):108621. doi: 10.1016/j.celrep.2020.108621.
Eosinophils mediate protection against filarial nematodes. Our results demonstrate that eosinophil extracellular traps (EETosis) are induced by microfilariae and infective L3 larvae of Litomosoides sigmodontis. These extracellular DNA traps inhibit microfilariae motility in a DNA- and contact-dependent manner in vitro. Accordingly, microfilariae-injection triggers DNA release in an eosinophil-dependent manner in vivo and microfilariae covered with DNA traps are cleared more rapidly. Using dectin-1, we identify the required receptor for the microfilariae-induced EETosis, whereas signaling via other C-type lectin receptors, prior priming of eosinophils, and presence of antibodies are not required. The DNA released upon microfilariae-induced EETosis is mainly of mitochondrial origin, but acetylated and citrullinated histones are found within the traps. We further demonstrate that the presented DNA-dependent inhibition of microfilariae motility by eosinophils represents a conserved mechanism, as microfilariae from L. sigmodontis and the canine heartworm Dirofilaria immitis induce ETosis in murine and human eosinophils.
嗜酸性粒细胞介导对抗丝虫的保护作用。我们的结果表明，微丝蚴和感染性 L3 幼虫的利什曼原虫诱导嗜酸性粒细胞细胞外诱捕（EETosis）。这些细胞外 DNA 诱捕物以 DNA 和接触依赖性方式在体外抑制微丝蚴的运动。因此，微丝蚴注射在体内以嗜酸性粒细胞依赖的方式触发 DNA 释放，并且被 DNA 诱捕物覆盖的微丝蚴被更快地清除。使用 dectin-1，我们确定了微丝蚴诱导的 EETosis 所需的受体，而其他 C 型凝集素受体的信号传导、嗜酸性粒细胞的预先启动以及抗体的存在不是必需的。微丝蚴诱导的 EETosis 释放的 DNA 主要来源于线粒体，但在诱捕物中发现了乙酰化和瓜氨酸化组蛋白。我们进一步证明，嗜酸性粒细胞通过 DNA 依赖性抑制微丝蚴运动代表一种保守机制，因为来自利什曼原虫和犬恶丝虫的微丝蚴诱导鼠和人嗜酸性粒细胞的 EETosis。
