Effect of Chlamydia trachomatis infection and subsequent tumor necrosis factor alpha secretion on apoptosis in the murine genital tract.
Effect of Chlamydia trachomatis infection and subsequent tumor necrosis factor alpha secretion on apoptosis in the murine genital tract.
复制标题
沙眼衣原体感染和随后的肿瘤坏死因子α分泌对小鼠生殖道细胞凋亡的影响。
DOI：
10.1128/iai.68.4.2237-2244.2000
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发表时间：
2000
影响因子：
3.1
通讯作者：
Ojcius,DM
中科院分区：
文献类型：
--
作者：
Perfettini,JL;Darville,T;Gachelin,G;Souque,P;Huerre,M;Dautry-Varsat,A;Ojcius,DM
在衣原体感染期间观察到的病理学最初是由于感染本身引起的局部组织损伤，随后是有害的宿主炎症反应，导致永久性瘢痕形成。我们最近报道了体外衣原体感染导致上皮细胞和巨噬细胞凋亡，感染的单核细胞分泌促炎细胞因子白细胞介素-1 β。同时，促炎细胞因子如肿瘤坏死因子α（TNF-α）也可触发易感细胞的凋亡。为了研究沙眼衣原体感染与体内细胞凋亡之间的可能关系，我们使用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记技术来确定感染是否可能导致小鼠生殖道细胞凋亡，反之，炎症反应过程中产生的细胞因子是否可能调节细胞凋亡水平。我们的研究结果表明，感染后第2天或第7天的宫颈内膜中的感染细胞有时会凋亡，尽管宫颈内膜中凋亡细胞的数量没有统计学显著变化。然而，在管腔中观察到大量凋亡感染细胞，表明凋亡细胞可能从宫颈内膜脱落。此外，在感染后2或7天，子宫角和输卵管中的凋亡细胞数量大量增加，并伴有明显的上尿路病理体征。有趣的是，TNF-α的耗竭导致感染7天的动物的子宫角和输卵管中的细胞凋亡水平降低，这表明炎性细胞因子可能通过感染组织中的细胞凋亡发挥其部分病理作用。
The pathology observed duringChlamydiainfection is due initially to localized tissue damage caused by the infection itself, followed by deleterious host inflammatory responses that lead to permanent scarring. We have recently reported that the infection byChlamydiain vitro results in apoptosis of epithelial cells and macrophages and that infected monocytes secrete the proinflammatory cytokine interleukin-1β. At the same time, proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) can also trigger apoptosis of susceptible cells. To study the possible relationship betweenChlamydia trachomatisinfection and apoptosis in vivo, we used the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling technique to determine whether infection may cause apoptosis in the genital tract of mice and, conversely, whether cytokines produced during the inflammatory response may modulate the level of apoptosis. Our results demonstrate that infected cells in the endocervix at day 2 or 7 after infection are sometimes apoptotic, although there was not a statistically significant change in the number of apoptotic cells in the endocervix. However, large clumps of apoptotic infected cells were observed in the lumen, suggesting that apoptotic cells may be shed from the endocervix. Moreover, there was a large increase in the number of apoptotic cells in the uterine horns and oviducts after 2 or 7 days of infection, which was accompanied by obvious signs of upper tract pathology. Interestingly, depletion of TNF-α led to a decrease in the level of apoptosis in the uterine horns and oviducts of animals infected for 7 days, suggesting that the inflammatory cytokines may exert part of their pathological effect via apoptosis in infected tissues.