Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, United States of America.
PLoS Biol. 2018 Feb 6;16(2):e2003885. doi: 10.1371/journal.pbio.2003885. eCollection 2018 Feb.
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.
阴道毛滴虫是一种感染人类的寄生虫，是全球最常见的非病毒性性传播感染（STI）病原体，可导致不良的炎症性疾病。目前对阴道毛滴虫的免疫反应知之甚少。中性粒细胞（多形核细胞[PMN]）是存在于阴道毛滴虫-宿主界面的主要免疫细胞，被认为可以清除阴道毛滴虫。然而，PMN 清除阴道毛滴虫的机制尚未得到阐明。我们证明，人中性粒细胞以剂量依赖性、接触依赖性和中性粒细胞胞外诱捕网（NET）独立的方式快速杀死阴道毛滴虫。与吞噬作用相反，我们观察到 PMN 杀死阴道毛滴虫涉及在寄生虫死亡之前对阴道毛滴虫进行“咬噬”，并利用胞饮作用来实现病原体杀伤。胞饮作用和寄生虫杀伤均依赖于 PMN 丝氨酸蛋白酶和人血清因子的存在。我们的分析首次证明了哺乳动物吞噬细胞利用胞饮作用清除病原体，并揭示了 PMN 杀死大型、高迁移性靶标的一种新机制。
