Treponema pallidum delays the apoptosis of human polymorphonuclear neutrophils through the intrinsic and extrinsic pathways
Treponema pallidum delays the apoptosis of human polymorphonuclear neutrophils through the intrinsic and extrinsic pathways
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DOI：
10.1016/j.molimm.2022.04.012
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发表时间：
2022-05-18
影响因子：
3.6
通讯作者：
Wu，Yimou
中科院分区：
文献类型：
--
作者：
Wang，Jianye;Lu，Simin;Wu，Yimou
梅毒螺旋体是一种引起传染性性传播疾病的“隐形病原体”。虽然中性粒细胞通常存在于早期梅毒的皮损中，但这些细胞的作用不明显。几乎没有人调查过梅毒螺旋体感染。中性粒细胞是经历结构性凋亡的短暂细胞，吞噬作用通常会加速这一过程。在这里，我们证明了人多形核中性粒细胞(HPMN)可以吞噬T。梅毒在体外。一个意想不到的发现是。苍白球能明显抑制hPMN的凋亡，且不依赖于调理素样作用。此外，这种现象不受细菌活性的影响，如Annexin V、形态学研究和TUNEL染色所检测的那样。对其机制的探讨表明，半胱氨酸天冬氨酸氨基转移酶-3、−-8和−-9的裂解形式的表达和效应蛋白半胱氨酸氨基转移酶的活性显著降低。梅毒螺旋体感染的hPMNs.T.梅毒螺旋体也削弱了星形孢子素和抗Fas诱导的中性粒细胞凋亡信号。值得注意的是，这些效应伴随着诱导抗凋亡细胞因子IL-8的自分泌产生。综上所述，我们的数据显示。苍白球可通过内源性和外源性途径抑制hPMN的凋亡，为进一步了解其致病机制提供了新的思路。梅毒。
Treponema pallidumis a “stealth pathogen” responsible for infectious sexually transmitted diseases. Although neutrophils are usually present in skin lesions of early syphilis, the role of these cells inT. palliduminfection has barely been investigated. Neutrophils are short-lived cells that undergo constitutive apoptosis, and phagocytosis usually accelerates this process. Here, we demonstrated that human polymorphonuclear neutrophils (hPMNs) could phagocytoseT. pallidum in vitro. An unexpected discovery was thatT. palliduminhibited hPMNs apoptosis markedly in an opsonin-independent manner. Furthermore, this phenomenon was not affected by bacterial viability, as detected by annexin V, morphology studies, and TUNEL staining. Exploration of the underlying mechanism showed that expression of the cleaved forms of caspase-3, −8, and −9 and effector caspase activity were diminished significantly inT. pallidum-infected hPMNs.T. pallidumalso impaired staurosporine- and anti-Fas-induced signaling for neutrophil apoptosis. Of note, these effects were accompanied by inducing the autocrine production of the anti-apoptotic cytokine IL-8. Taken together, our data revealed thatT. pallidumcould inhibit the apoptosis of hPMNs through intrinsic and extrinsic pathways and provide new insights for understanding the pathogenicity mechanisms ofT. pallidum.