The outer membrane protein Tp92 of Treponema pallidum delays human neutrophil apoptosis via the ERK, PI3K/Akt, and NF-?B pathways
The outer membrane protein Tp92 of Treponema pallidum delays human neutrophil apoptosis via the ERK, PI3K/Akt, and NF-?B pathways
复制标题
DOI：
10.1111/mmi.15164
复制
发表时间：
2023-09-17
影响因子：
3.6
通讯作者：
Wu，Yimou
中科院分区：
文献类型：
--
作者：
Li，Weiwei;Li，Sijia;Wu，Yimou
梅毒是一种持续性的性传播疾病，由难以捉摸的病原体梅毒螺旋体的渗透引起。尽管人类多形核中性粒细胞（hPMN）在皮肤病变中的流行，这是早期梅毒的特征，但它们在苍白球滴虫感染中的作用仍不清楚。TP 92是唯一的T。苍白球螺旋外膜蛋白，其表现出与其他革兰氏阴性细菌中的外膜蛋白相似的结构特征。然而，这种蛋白在免疫细胞中的功能机制仍不清楚。中性粒细胞是短寿命细胞，其响应于通常影响该过程的外部刺激而经历先天性凋亡。在这项研究中，我们确定了Tp 92通过ERK MAPK、PI 3 K/Akt和NF-κB信号通路阻碍了caspase-3的活化，从而抑制了hPMN内caspase-3的活性，从而防止了hPMN凋亡。此外，Tp 92还可以通过增强抗凋亡蛋白Mcl-1的表达，刺激IL-8的分泌，并保持线粒体膜电位来调节hPMN的凋亡。这些发现为T的分子机制提供了有价值的见解。palliduminfection和梅毒治疗建议潜在的治疗靶点。
Syphilis is a persistent sexually transmitted disease caused by infiltration of the elusive pathogenTreponema pallidum. Despite the prevalence of human polymorphonuclear neutrophils (hPMNs) within cutaneous lesions, which are characteristic of incipient syphilis, their role inT. palliduminfection remains unclear. Tp92 is the onlyT. pallidumhelical outer membrane protein that exhibits structural features similar to those of outer membrane proteins in other gram‐negative bacteria. However, the functional mechanism of this protein in immune cells remains unclear. Neutrophils are short‐lived cells that undergo innate apoptosis in response to external stimuli that typically influence this process. In this study, we determined that Tp92 impedes the activation of procaspase‐3 via the ERK MAPK, PI3K/Akt, and NF‐κB signaling pathways, consequently suppressing caspase‐3 activity within hPMNs, and thereby preventing hPMNs apoptosis. Furthermore, Tp92 could also modulate hPMNs apoptosis by enhancing the expression of the anti‐apoptotic protein Mcl‐1, stimulating IL‐8 secretion, and preserving the mitochondrial membrane potential. These findings provide valuable insights into the molecular mechanisms underlyingT. palliduminfection and suggest potential therapeutic targets for syphilis treatment.