CYTOKINE NETWORK IN CHLAMYDIAL DISEASE

描述（改编自申请人的摘要）：在女性中， C的表现。沙眼感染范围从无症状的宫颈炎 盆腔炎、不孕症和宫外孕。变化 结果表明，人类在宿主易感性方面表现出异质性 衣原体病支持遗传对疾病易感性的影响 通过对人类和实验动物模型的流行病学研究， 感染候选人已经证实，三个人之间存在真正的差异。 关于生殖器衣原体消退的遗传定义的小鼠品系 肠道感染和病理后遗症的发展。尽管有这些 差异，广泛的数据显示，他们的获得性免疫反应是 类似的-Th 1表型的CD 4 + T细胞对于从 衣原体感染相比之下，比较活动期间的反应 感染的第一周揭示了早期细胞和 细胞因子反应介质。这项建议涉及使用固有的 这些小鼠品系中存在的差异作为检查细胞因子的工具 在衣原体疾病发病机制中重要的调节途径。的 不同类型的细胞因子反应的显著性 这三种菌株将在遗传缺陷的小鼠中进一步研究， 特异性细胞因子介质。该提案的具体目标包括： 确认TNF-α和中性粒细胞在早期控制 衣原体感染和确定其在发展中的作用 慢性病理学; 2）描述其他促炎性疾病的贡献 细胞因子（白细胞介素-1和白细胞介素-6）和选择趋化因子的宿主 防御和免疫病理学; 3）确定是否有不同的动力学， 下调细胞因子TGF-β和白细胞介素-10影响病程， 衣原体生殖道感染的结果。细胞因子的测定 反应模式，促进组织损伤，从那些导致良性 解决感染问题是一个重要的目标， 安全有效的衣原体疫苗。

DESCRIPTION (Adapted from the Applicant's Abstract): In women, the manifestations of C. trachomatis infection range from asymptomatic cervicitis to pelvic inflammatory disease, infertility, and ectopic pregnancy. Variations in outcomes suggest humans exhibit heterogeneity in host susceptibility to chlamydial disease. A genetic influence on disease susceptibility is supported by epidemiological studies in humans, and in animal models of experimental infection. The candidate has confirmed that true differences exist among three genetically defined strains of mice as regards resolution of chlamydial genital tract infection and the development of pathological sequelae. Despite these differences, extensive data reveal their acquired immune responses to be similar - CD4+ T cells of the Th 1 phenotype are critical to recovery from chlamydial infection. In contrast, comparisons of responses active during the first week of infection reveal significant differences in early cellular and cytokine response mediators. This proposal involves using the inherent differences present in these strains of mice as a tool for examining cytokine regulatory pathways important in chlamydial disease pathogenesis. The significance of the different patterns of cytokine responses determined among the three strains will be further explored with mice genetically deficient in specific cytokine mediators. Specific aims of the proposal include: 1) confirmation of the role of TNF-alpha and of neutrophils in early control of chlamydial infection and determination of their role in the development of chronic pathology; 2) delineation of the contribution of other proinflammatory cytokines (interleukin-1 and interleukin-6) and of select chemokines to host defense and immunopathology; 3) determination if different kinetics of the downregulatory cytokines, TGF-beta and interleukin-10, influence the course and outcome of chlamydial genital tract infection. A determination of cytokine response patterns that promote tissue damage from those that result in benign resolution of infection is an important goal as regards the development of a safe and effective chlamydial vaccine.