Kaushic C, Murdin A D, Underdown B J, Wira C R
Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001, USA.
Infect Immun. 1998 Mar;66(3):893-8. doi: 10.1128/IAI.66.3.893-898.1998.
As the most common cause of sexually transmitted disease in women, chlamydial infections can lead to pelvic inflammatory disease, infertility, and ectopic pregnancy. To better understand the role played by sex hormones in modulating the immune response of the genital tract to microbial infections, we have developed a rat model to study Chlamydia trachomatis infection. Inbred female Lewis rats were primed with progesterone and inoculated by intrauterine instillation of C. trachomatis (mouse pneumonitis strain MoPn) into each uterine horn. When infected animals were examined for the presence of chlamydial antigens 14 days postinfection, both the uterus and vagina were found to be positive compared to those of saline-treated animals, which did not show specific staining. The involvement of local and systemic immune systems following chlamydial infection was determined by analyzing major histocompatibility complex (MHC) class II expression in the reproductive tract and lymphocyte proliferation in response to mitogenic and chlamydia-specific stimulation of cells from the spleen and lymph nodes (LN) draining the reproductive tract. Enhanced proliferation was observed in LN following mitogenic but not antigenic (MOMP [major outer membrane protein]) stimulation. In contrast, spleen cell proliferation was lower in chlamydia-infected rats than in saline-treated controls. MHC class II expression, an indicator of inflammatory responses, was upregulated in the uterus, on glandular epithelial cells, and adjacent to glands in response to chlamydial infection. In other experiments, when rats were infected at estrus and diestrus without prior progesterone priming, chlamydial inclusions were not detected in either the uterus or vagina. However, enhanced lymphocyte proliferation was observed in response to mitogenic and MOMP stimulation in the reproductive tract-draining LN from estrous and diestrous animals. These findings indicate that under appropriate endocrine conditions, the rat uterus is susceptible to C. trachomatis infection and that immune responses to this pathogen can be detected locally and systemically. Further, they suggest that clearance of the infection from the reproductive tract involves immune cells from the LN draining the reproductive tract.
作为女性性传播疾病最常见的病因，衣原体感染可导致盆腔炎、不孕和异位妊娠。为了更好地理解性激素在调节生殖道对微生物感染的免疫反应中所起的作用，我们建立了一个大鼠模型来研究沙眼衣原体感染。将近交系雌性Lewis大鼠用孕酮预处理，然后通过向每个子宫角宫内滴注沙眼衣原体（小鼠肺炎菌株MoPn）进行接种。感染动物在感染后14天检查衣原体抗原的存在情况时，发现子宫和阴道均呈阳性，而生理盐水处理的动物则未显示特异性染色。通过分析生殖道中主要组织相容性复合体（MHC）II类分子的表达以及对来自脾脏和引流生殖道的淋巴结（LN）的细胞进行促有丝分裂和衣原体特异性刺激后淋巴细胞的增殖情况，来确定衣原体感染后局部和全身免疫系统的参与情况。在促有丝分裂刺激后，LN中观察到增殖增强，但在抗原（主要外膜蛋白[MOMP]）刺激后未观察到。相反，衣原体感染大鼠的脾细胞增殖低于生理盐水处理的对照组。作为炎症反应指标的MHC II类分子表达，在衣原体感染后子宫内的腺上皮细胞及其相邻腺体处上调。在其他实验中，当大鼠在发情期和动情间期未经孕酮预处理而被感染时，在子宫或阴道中均未检测到衣原体包涵体。然而，在发情期和动情间期动物引流生殖道的LN中，对促有丝分裂和MOMP刺激的反应中观察到淋巴细胞增殖增强。这些发现表明，在适当的内分泌条件下，大鼠子宫易受沙眼衣原体感染，并且可以在局部和全身检测到对该病原体的免疫反应。此外，它们表明从生殖道清除感染涉及引流生殖道的LN中的免疫细胞。
