生殖道衣原体传播至胃肠道并靶向诱导输卵管病变——双重攻击模式

Chlamydia transmitting from the genital to gastrointestinal tract and inducing tubal disease:Double attack pattern

沙眼衣原体(Chlamydia trachomatis,CT)生殖道感染较为隐匿,患者常无自觉症状,感染后延误治疗的女性可导致严重的并发症。鼠型衣原体(Chlamydia muridarum,CM)感染小鼠生殖道可模拟CT感染女性生殖道,是研究CT发病机制的理想模型。CM质粒蛋白pGP3、染色体蛋白TC0237/TC0668、CM特异性CD8~+T细胞和细胞因子TNF-α、IL-13能够诱导生殖道炎症,CD4^(+)T细胞则负责清除CM。然而,生殖道CM被清除后,输卵管炎症仍持续存在。生殖道CM可自行播散至胃肠道,胃肠道CM不能逆向返回生殖道。生殖道传播至胃肠道的CM在胃肠道存活的时间和数量与输卵管长期病变呈正相关,而直接接种至胃肠道的CM对生殖道与胃肠道均无致病性。衣原体致生殖道长期炎症反应的双重攻击模式被提出:CM感染生殖道输卵管上皮细胞后启动输卵管修复过程为首次攻击;生殖道CM传播至胃肠道后,活化的衣原体特异性CD8^(+)T细胞被募集至生殖道,分泌促纤维化细胞因子如TNF-α和IL-13为二次攻击,将首次攻击启动的输卵管修复转化为长期输卵管纤维化/积水。研究衣原体感染的致病机制可为衣原体疫苗研发提供新思路,并为解决女性因CT反复感染导致不孕等问题提供参考依据。

Chlamydia trachomatis(CT)genital tract infection is insidious,and patients often have no conscious symptoms.Delayed treatment after infection can lead to serious complications.Chlamydia muridarum(CM)genital tract infection in female mice can simulate CT genital tract infection in women,which is an ideal model to investigate the pathogenesis of CT.CM plasmid protein pGP3,chromosomal protein TC0237/TC0668,CM-specific CD8T cells,TNF-α,and IL-13 can induce genital tract inflammation,CD4^(+)T cells are responsible for CM clearance.However,tubal inflammation persists after genital tract CM is removed.Genital tract CM can spread spontaneously in vivo and colonize the gastrointestinal(GI)tract,but the GI tract CM cannot reverse spread to the genital tract.The survival time and number of CM transmitted from genital tract to GI tract are positively correlated with the long-term lesion of oviduct,while the CM inoculated directly into the GI tract has no pathogenicity in both the genital and GI tract.The double attack pattern of Chlamydiainduced genital tract inflammatory lesions is as follows:CM infection of oviduct epithelial cells initiates the process of oviduct repair as the first attack.After genital CM spreads to the GI tract,activated chlamydia-specific CD8^(+)T cells are recruited to the genital tract and secreted pro-fibrotic cytokines such as TNF-α and IL-13.This process is called the second attack which transform tubal repair initiated by the first attack into long-term tubal fibrosis/hydrosalpinx.Elucidating the pathogenic mechanism of Chlamydia infection can provide new ideas for the development of Chlamydia vaccine,which is expected to solve the problems of infertility caused by repeated CT infection in women.