Modulation of phagocytosis‐induced cell death of human neutrophils by Neisseria gonorrhoeae,Journal of Leukocyte Biology

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Modulation of phagocytosis‐induced cell death of human neutrophils by Neisseria gonorrhoeae
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-09-25 , DOI: 10.1002/jlb.4ma0820-649r
Christine Cho ₁ , Athmane Teghanemt ₁ , Michael A. Apicella ₂ , William M. Nauseef _{1,

2}

Affiliation

Optimal innate immune response to infection includes eradication of potential pathogens, resolution of associated inflammation, and restitution of homeostasis. Phagocytosing human polymorphonuclear leukocytes (hPMN) undergo accelerated apoptosis, a process referred to as phagocytosis‐induced cell death (PICD) and an early step in their clearance from inflammatory sites. Among human pathogens that modulate hPMN apoptosis, Neisseria gonorrhoeae delays PICD, which may contribute to the exuberant neutrophilic inflammation that characterizes gonorrhea. To elucidate the mechanisms underlying delayed PICD, we compared features of hPMN cell death that followed phagocytosis of N. gonorrhoeae FA1090 wild‐type (GC) or serum‐opsonized zymosan (OPZ), a prototypical stimulus of PICD. Phosphatidylserine externalization required NADPH oxidase activity after ingestion of GC or OPZ, and annexin V staining and DNA fragmentation were less after phagocytosis of GC compared to OPZ. Caspase 3/7 and caspase 9 activities after phagocytosis of GC were less than that seen after ingestion of OPZ, but caspase 8 activity was the same after ingestion of GC or OPZ. When hPMN sequentially ingested GC followed by OPZ, both caspase 3/7 and 9 activities were less than that seen after OPZ alone, and the inhibition was dose dependent for GC, suggesting that ingestion of GC actively inhibited PICD. Sequential phagocytosis did not block caspase 8 activity, mitochondrial depolarization, or annexin V/propidium iodide staining compared to responses of hPMN fed OPZ alone, despite inhibition of caspases 3/7 and 9. Taken together, these data suggest that active inhibition of the intrinsic pathway of apoptosis contributes to the delay in PICD after hPMN ingestion of N. gonorrhoeae.

中文翻译：

淋病奈瑟氏球菌对吞噬作用诱导的人类嗜中性白细胞死亡的调节

对感染的最佳先天免疫反应包括根除潜在的病原体，解决相关的炎症以及恢复体内平衡。吞噬人类多形核白细胞（hPMN）会加速凋亡，这一过程被称为吞噬作用诱导的细胞死亡（PICD），是其从炎症部位清除的早期步骤。在调节hPMN凋亡的人类病原体中，淋病奈瑟氏球菌会延迟PICD，这可能会导致淋病特征性旺盛的嗜中性粒细胞炎症。为了阐明延迟PICD的机制，我们比较了淋病奈瑟菌吞噬后hPMN细胞死亡的特征。FA1090野生型（GC）或血清调理的酵母聚糖（OPZ），这是PICD的典型刺激。吞噬GC或OPZ后，磷脂酰丝氨酸的外在化需要NADPH氧化酶活性，与OPZ相比，吞噬GC后膜联蛋白V染色和DNA片段化较少。吞噬GC后caspase 3/7和caspase 9的活性低于摄取OPZ后所见，但摄取GC或OPZ后caspase 8的活性相同。当hPMN先后摄取GC和OPZ后，胱天蛋白酶3/7和9的活性均低于单独服用OPZ后的活性，并且抑制作用与GC有关，这与GC的剂量依赖性有关，这表明摄取GC可以有效抑制PICD。顺序吞噬作用并未阻止caspase 8活性，线粒体去极化，淋病奈瑟氏球菌。

更新日期：2020-10-30

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