Neisseria gonorrhoeae-Mediated Inhibition of Apoptotic Signalling in Polymorphonuclear Leukocytes
Neisseria gonorrhoeae-Mediated Inhibition of Apoptotic Signalling in Polymorphonuclear Leukocytes
复制标题
DOI：
10.1128/iai.01267-10
复制
发表时间：
2011-11-01
影响因子：
3.1
通讯作者：
Seifert, H. Steven
中科院分区：
文献类型：
--
作者：
Chen, Adrienne;Seifert, H. Steven
人类病原体淋病奈瑟菌在感染期间招募并广泛与多形核白细胞(PMN)相互作用。淋病奈瑟菌能够存活在这些先天免疫细胞的杀菌活性中，并能在体外主动调节PMN功能。中性粒细胞是一种易发生凋亡的短命细胞，因此淋病奈瑟菌感染对中性粒细胞存活的影响对于中性粒细胞在感染过程中是否可能是细菌复制的重要部位具有重要意义。我们建立并验证了中性粒细胞感染的HL-60髓系白血病细胞培养模型，并使用这些细胞和原代PMN来证明淋球菌单独感染不能诱导细胞凋亡，而且淋球菌可以抑制自发性凋亡和内源性和外源性凋亡诱导剂星形孢子素(STS)和肿瘤坏死因子(TNF)相关的凋亡诱导配体(TRAIL)诱导的凋亡。淋球菌感染还导致中性粒细胞中核因子-kappa B信号的激活，并诱导HL-60细胞和原代PMN分泌相同的促炎细胞因子和趋化因子。我们的数据表明，HL-60细胞系可以有效地模拟淋球菌与中性粒细胞的相互作用，淋球菌可以主动抑制多种刺激诱导的细胞凋亡，以延长中性粒细胞的存活时间，并潜在地促进细菌的生存、复制和传播。
The human pathogen Neisseria gonorrhoeae recruits and interacts extensively with polymorphonuclear leukocytes (PMNs) during infection. N. gonorrhoeae is able to survive the bactericidal activity of these innate immune cells and can actively modulate PMN functions in vitro. PMNs are short-lived cells which readily undergo apoptosis, and thus the effect of N. gonorrhoeae infection on PMN survival has implications for whether PMNs might serve as an important site of bacterial replication during infection. We developed and validated an HL-60 myeloid leukemia cell culture model for PMN infection and used both these cells and primary PMNs to show that N. gonorrhoeae infection alone does not induce apoptosis and furthermore that N. gonorrhoeae can inhibit both spontaneous apoptosis and apoptosis induced by the intrinsic and extrinsic apoptosis inducers staurosporine (STS) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), respectively. N. gonorrhoeae infection also results in the activation of NF-kappa B signaling in neutrophils and induces secretion of an identical profile of proinflammatory cytokines and chemokines in both HL-60 cells and primary PMNs. Our data show that the HL-60 cell line can be used to effectively model N. gonorrhoeae-PMN interactions and that N. gonorrhoeae actively inhibits apoptosis induced by multiple stimuli to prolong PMN survival and potentially facilitate bacterial survival, replication, and transmission.