Chen Xi, Liu Luyao, Zhang Xu, Lu Chunxue, Chen Li, Quan Shufen, Chen Lili
School of Public Health, University of South China, Hengyang 421001, China.
Hengyang Key Laboratory for Health Hazard Factors Inspection and Quarantine, Hengyang 421001, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2020 Mar 30;40(3):388-393. doi: 10.12122/j.issn.1673-4254.2020.03.17.
To explore the role of tumor necrosis factor-α (TNF-α) in immune response to urogenital chlamydial infection and urogenital pathology in mice.
Fifteen female wild-type (WT) C57BL/6J mice and 15 TNF-α receptor knockout (TNF-αR KO) mice were inoculated intravaginally with 1×10 inclusion forming units (IFUs) of live . At 56 days after the first inoculation, 8 mice from each group were subjected to a second inoculation at the same dose. Vaginal swabs were taken every 3 or 4 days to detect the number of inclusion bodies of chlamydia. On day 80 after the first inoculation, the mice were euthanized and peritoneal macrophages were collected and the vaginal tract and spleen were dissected. The pathologies in the fallopian tube and the uterine horn were observed and the severity of inflammatory cell infiltration and lumen dilatation were semi-quantitatively scored. The levels of interleukin-6 (IL-6), IL-8, IL-1α, IL-1β and TNF-α in the supernatant of the peritoneal macrophage were detected. Spleen cell suspension was prepared, and after stimulation with chlamydia EB , the levels of the cytokines including IL-4, IL-5, IL-17 and interferon-γ (IFN-γ) were determined in the cells.
The clearance rate of from the urogenital tract was similar between TNF-αR KO mice and WT mice regardless of the primary or second infection. The severity of inflammation in the fallopian tube and the uterine horn did not differ significantly between the two groups, but TNF-αR KO mice had significantly milder dilation of the fallopian tubes ( < 0.05). The peritoneal macrophages from TNF-αR KO mice produced a significantly higher level of TNF-α than those from WT mice ( < 0.05); the spleen cells from the two groups both produced high levels of IFN-γ, but IL-17 production by the spleen cells was significantly lower in TNF-αR KO mice than in WT mice ( < 0.05).
TNF-α is not associated with protective immune response against infection, and can worsen the inflammatory damages of the urogenital tract caused by in mice.
探讨肿瘤坏死因子-α（TNF-α）在小鼠泌尿生殖系统衣原体感染免疫反应及泌尿生殖系统病理变化中的作用。
将15只雌性野生型（WT）C57BL/6J小鼠和15只TNF-α受体敲除（TNF-αR KO）小鼠经阴道接种1×10个活沙眼衣原体包涵体形成单位（IFUs）。首次接种后56天，每组8只小鼠以相同剂量进行第二次接种。每3或4天采集阴道拭子检测衣原体包涵体数量。首次接种后80天，对小鼠实施安乐死，收集腹腔巨噬细胞并解剖阴道和脾脏。观察输卵管和子宫角的病理变化，对炎症细胞浸润和管腔扩张的严重程度进行半定量评分。检测腹腔巨噬细胞上清液中白细胞介素-6（IL-6）、IL-8、IL-1α、IL-1β和TNF-α的水平。制备脾细胞悬液，用衣原体EB刺激后，测定细胞中包括IL-4、IL-5、IL-17和干扰素-γ（IFN-γ）在内的细胞因子水平。
无论初次感染还是二次感染，TNF-αR KO小鼠和WT小鼠泌尿生殖道沙眼衣原体的清除率相似。两组输卵管和子宫角的炎症严重程度无显著差异，但TNF-αR KO小鼠输卵管扩张明显较轻（P<0.05）。TNF-αR KO小鼠的腹腔巨噬细胞产生的TNF-α水平显著高于WT小鼠（P<0.05）；两组脾细胞均产生高水平的IFN-γ，但TNF-αR KO小鼠脾细胞产生的IL-17明显低于WT小鼠（P<0.05）。
TNF-α与小鼠抗沙眼衣原体感染的保护性免疫反应无关，且可加重小鼠泌尿生殖道由沙眼衣原体引起的炎症损伤。
