Neutrophils kill the parasite Trichomonas vaginalis using trogocytosis.
Neutrophils kill the parasite Trichomonas vaginalis using trogocytosis.
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DOI：
10.1371/journal.pbio.2003885
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发表时间：
2018-03
期刊：
影响因子：
9.8
通讯作者：
Johnson PJ
中科院分区：
文献类型：
--
作者：
Mercer F;Ng SH;Brown TM;Boatman G;Johnson PJ
t.迷走神经炎是一种人类感染性寄生虫，在世界范围内引起最常见的非病毒性性传播感染（STI），并导致不良炎症性疾病。T.对迷走神经的了解很少。中性粒细胞（多形核白细胞[PMNs]）是T细胞中主要的免疫细胞。阴道-宿主界面，并被认为是清除T.流浪汉T.迷走神经尚未被定性。我们证明了人的中性粒细胞迅速杀死T。以剂量依赖性、接触依赖性和中性粒细胞胞外陷阱（NET）非依赖性方式抑制迷走神经。与吞噬作用相反，我们观察到T.迷走性行为包括"咬" T。寄生虫死亡前的迷走神经，利用胞刺作用实现病原体杀灭。胞啃作用和寄生虫杀伤都依赖于PMN丝氨酸蛋白酶和人血清因子的存在。我们的分析提供了第一个演示，据我们所知，哺乳动物的吞噬细胞使用trogocytosis病原体清除，并揭示了一种新的机制所使用的中性粒细胞杀死一个大的，高度能动的目标。人类寄生虫阴道毛滴虫是一种大型单细胞，能动的真核生物，导致人类高度流行的性传播感染：滴虫病。虽然滴虫病的有害影响与炎症有关，但对寄生虫的免疫反应严重不足。嗜中性粒细胞在宿主对T.寄生虫，但以前并不知道它们在杀死寄生虫方面的有效性以及它们用于这样做的机制。在这里，我们表明，人类中性粒细胞使用胞刺，一个以前未描述的嗜中性粒细胞模式的微生物杀死，杀死T。流浪汉胞吞作用是细胞"咬"邻近细胞的过程，该过程也被称为"蚕食"。使用3D和4D实时成像，我们发现中性粒细胞迅速包围并胞吞T。寄生虫死亡前的迷走神经我们排除了整个寄生虫吞噬（吞噬作用）和就业的中性粒细胞胞外陷阱（NETosis）在这种快速的接触依赖性杀伤。我们还表明，抗体片段可结晶（Fc）受体的相互作用介导的嗜中性粒细胞胞啃和杀伤和丝氨酸蛋白酶，通常采用的嗜中性粒细胞的微生物降解，另外发挥作用，寄生虫“啃”。
T. vaginalis, a human-infective parasite, causes the most common nonviral sexually transmitted infection (STI) worldwide and contributes to adverse inflammatory disorders. The immune response to T. vaginalis is poorly understood. Neutrophils (polymorphonuclear cells [PMNs]) are the major immune cell present at the T. vaginalis–host interface and are thought to clear T. vaginalis. However, the mechanism of PMN clearance of T. vaginalis has not been characterized. We demonstrate that human PMNs rapidly kill T. vaginalis in a dose-dependent, contact-dependent, and neutrophil extracellular trap (NET)-independent manner. In contrast to phagocytosis, we observed that PMN killing of T. vaginalis involves taking “bites” of T. vaginalis prior to parasite death, using trogocytosis to achieve pathogen killing. Both trogocytosis and parasite killing are dependent on the presence of PMN serine proteases and human serum factors. Our analyses provide the first demonstration, to our knowledge, of a mammalian phagocyte using trogocytosis for pathogen clearance and reveal a novel mechanism used by PMNs to kill a large, highly motile target. The human parasite Trichomonas vaginalis is a large unicellular, motile eukaryote that causes a highly prevalent sexually transmitted infection in humans: trichomoniasis. While harmful effects of trichomoniasis are associated with inflammation, the immune response to the parasite is sorely under-characterized. Neutrophils are known to be important players in the host response to T. vaginalis, but it was not previously known how effective they are at killing the parasite and the mechanism(s) they use to do this. Here, we show that human neutrophils use trogocytosis, a previously undescribed neutrophil mode of microbial killing, to kill T. vaginalis. Trogocytosis is a process by which a cell takes “bites” of a neighboring cell, a process also referred to as “nibbling.” Using 3D and 4D live imaging, we show that neutrophils rapidly surround and trogocytose T. vaginalis, prior to parasite death. We rule out whole parasite engulfment (phagocytosis) and the employment of neutrophil extracellular traps (NETosis) in this rapid contact-dependent killing. We also show that antibody–fragment crystallizable (Fc) receptor interactions mediate neutrophil trogocytosis and killing and that serine proteases, commonly employed by neutrophils for microbial degradation, additionally play a role in parasite “nibbling”.
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影响因子：
3.4
作者：
Fichorova, Raina N.
通讯作者：
Fichorova, Raina N.
DOI：
10.1073/pnas.0900226106
发表时间：
2009-04-21
影响因子：
11.1
作者：
Guimaraes-Costa, Anderson B.;Nascimento, Michelle T. C.;Saraiva, Elvira M.
通讯作者：
Saraiva, Elvira M.
影响因子：
7.3
作者：
Dhainaut M;Moser M
通讯作者：
Moser M
影响因子：
--
作者：
Arroyo R;Cárdenas-Guerra RE;Figueroa-Angulo EE;Puente-Rivera J;Zamudio-Prieto O;Ortega-López J
通讯作者：
Ortega-López J
影响因子：
6.4
作者：
Clark, RA
通讯作者：
Clark, RA