Muñoz-Caro Tamara, Silva Liliana M R, Ritter Christin, Taubert Anja, Hermosilla Carlos
Institute of Parasitology, BFS, Justus Liebig University Giessen, Schubertstraße 81, 35392, Giessen, Germany.
Parasitol Res. 2014 Nov;113(11):4189-97. doi: 10.1007/s00436-014-4094-3. Epub 2014 Sep 6.
Extracellular trap (ET) formation has been demonstrated as an important novel effector mechanism of polymorphonuclear neutrophils (PMN), eosinophils, mast cells and macrophages acting extracellularly against pathogens. In the present study, we show that tachyzoites of the emerging apicomplexan parasite Besnoitia besnoiti, that have recently been reported as potent inducers of PMN-derived ETosis, also trigger the release of ETs in an additional cell type, namely in monocytes. Fluorescence illustrations as well as scanning electron microscopy analyses (SEM) showed monocyte-promoted ET formation to be rapidly induced upon exposure to viable tachyzoites of B. besnoiti. Classical characteristics of ETs were confirmed by the co-localization of extracellular DNA with histones (H3) or myeloperoxidase (MPO) in parasite-entrapping structures. Monocyte-derived ETs were efficiently abolished by DNase I treatment and significantly reduced by treatments with inhibitors of MPO and NADPH oxidase, thus strengthening the key roles of reactive oxygen species (ROS) and MPO in monocyte ET formation. For comparative reasons, we additionally tested sporozoite stages of the closely related parasite Eimeria bovis for their capacity to induce monocyte-derived ETs and showed that these stages indeed induce ETs. To our best knowledge, we here report for the first time on monocyte ETs against the apicomplexan parasites B. besnoiti and E. bovis. Our results indicate that monocyte-triggered ETs may represent an important effector mechanism of the host early innate immune response against B. besnoiti and add a new cell type to the list of cells capable to release ETs.
细胞外陷阱(ET)形成已被证明是多形核中性粒细胞(PMN)、嗜酸性粒细胞、肥大细胞和巨噬细胞在细胞外对抗病原体的一种重要的新型效应机制。在本研究中,我们发现新出现的顶复门寄生虫贝斯诺球虫(Besnoitia besnoiti)的速殖子,最近被报道为PMN源性ETosis的有效诱导剂,它也能在另一种细胞类型即单核细胞中触发ET的释放。荧光图像以及扫描电子显微镜分析(SEM)显示,暴露于贝斯诺球虫的活速殖子后,单核细胞促进的ET形成会迅速被诱导。通过细胞外DNA与组蛋白(H3)或髓过氧化物酶(MPO)在捕获寄生虫结构中的共定位,证实了ET的典型特征。用DNase I处理可有效消除单核细胞衍生的ET,用MPO和NADPH氧化酶抑制剂处理可显著减少ET,从而强化了活性氧(ROS)和MPO在单核细胞ET形成中的关键作用。出于比较的原因,我们还测试了密切相关的寄生虫牛艾美耳球虫(Eimeria bovis)的子孢子阶段诱导单核细胞衍生ET的能力,并表明这些阶段确实能诱导ET。据我们所知,我们首次报道了针对顶复门寄生虫贝斯诺球虫和牛艾美耳球虫的单核细胞ET。我们的结果表明,单核细胞触发的ET可能代表宿主针对贝斯诺球虫早期固有免疫反应的一种重要效应机制,并为能够释放ET的细胞列表增加了一种新的细胞类型。