CYTOKINE NETWORK IN CHLAMYDIAL DISEASE

描述（改编自申请人的摘要）：在女性中， 沙眼衣原体感染的表现包括无症状宫颈炎 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 衣原体疾病。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。候选人已证实三者之间存在真正的差异 关于解决生殖器衣原体问题的基因定义的小鼠品系 道感染和病理后遗症的发展。尽管有这些 差异，大量数据表明他们获得的免疫反应是 类似 - Th 1 表型的 CD4 T 细胞对于从 衣原体感染。相比之下，在 感染第一周揭示了早期细胞和 细胞因子反应介质。该提案涉及使用固有的 这些小鼠品系中存在的差异作为检查细胞因子的工具 调节途径在衣原体疾病发病机制中很重要。的 确定的细胞因子反应不同模式的重要性 将用基因缺陷的小鼠进一步研究这三种品系 特异性细胞因子介质。该提案的具体目标包括：1) 证实 TNF-α 和中性粒细胞在早期控制中的作用 衣原体感染及其在疾病发展中的作用的测定 慢性病理学； 2) 描述其他促炎物质的贡献 细胞因子（白细胞介素 1 和白细胞介素 6）和宿主选择的趋化因子 防御和免疫病理学； 3) 确定不同的动力学 下调细胞因子 TGF-β 和白细胞介素 10，影响病程和 衣原体生殖道感染的结果。细胞因子的测定 促进组织损伤的反应模式与导致良性病变的反应模式 解决感染问题是发展新型冠状病毒感染的一个重要目标 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.