Key Points IL-1α drives oviduct pathology during genital Chlamydia infection in mice. IL-1α promotes neutrophil recruitment to the genital tract. Infection increases IL-1α expression in genital tract epithelial cells. Chlamydia trachomatis infection of the female genital tract can lead to irreversible fallopian tube scarring. In the mouse model of genital infection using Chlamydia muridarum, IL-1R signaling plays a critical role in oviduct tissue damage. In this study, we investigated the pathologic role of IL-1α, one of the two proinflammatory cytokines that bind to IL-1R. Il1a−/− mice infected with C. muridarum cleared infection at their cervix at the same rate as wild-type (WT) mice, but were significantly protected from end point oviduct damage and fibrosis. The contribution of IL-1α to oviduct pathology was more dramatic than observed in mice deficient for IL-1β. Although chlamydial burden was similar in WT and Il1a−/− oviduct during peak days of infection, levels of IL-1β, IL-6, CSF3, and CXCL2 were reduced in Il1a−/− oviduct lysates. During infection, Il1a−/− oviducts and uterine horns exhibited reduced neutrophil infiltration, and this reduction persisted after the infection resolved. The absence of IL-1α did not compromise CD4 T cell recruitment or function during primary or secondary chlamydial infection. IL-1α is expressed predominantly by luminal cells of the genital tract in response to infection, and low levels of expression persisted after the infection cleared. Ab-mediated depletion of IL-1α in WT mice prevented infection-induced oviduct damage, further supporting a key role for IL-1α in oviduct pathology.

中文翻译：

---

IL-1α 对小鼠生殖器衣原体感染期间的输卵管病理学至关重要

关键点 IL-1α 在小鼠生殖器衣原体感染期间驱动输卵管病理学。IL-1α 促进中性粒细胞向生殖道募集。感染会增加生殖道上皮细胞中 IL-1α 的表达。女性生殖道沙眼衣原体感染可导致不可逆的输卵管瘢痕形成。在使用鼠衣原体进行生殖器感染的小鼠模型中，IL-1R 信号传导在输卵管组织损伤中起关键作用。在这项研究中，我们研究了 IL-1α 的病理作用，IL-1α 是与 IL-1R 结合的两种促炎细胞因子之一。感染 C. muridarum 的 Il1a-/- 小鼠在其宫颈清除感染的速度与野生型 (WT) 小鼠相同，但受到终点输卵管损伤和纤维化的显着保护。IL-1α 对输卵管病理学的贡献比在缺乏 IL-1β 的小鼠中观察到的更为显着。尽管在感染高峰期 WT 和 Il1a-/- 输卵管的衣原体负荷相似，但 Il1a-/- 输卵管裂解物中 IL-1β、IL-6、CSF3 和 CXCL2 的水平降低。在感染期间，Il1a-/- 输卵管和子宫角表现出中性粒细胞浸润减少，并且这种减少在感染解决后持续存在。在原发性或继发性衣原体感染期间，IL-1α 的缺失不会影响 CD4 T 细胞的募集或功能。IL-1α 主要由生殖道腔细胞响应感染表达，并且在感染清除后持续低水平表达。Ab介导的WT小鼠中IL-1α的消耗阻止了感染引起的输卵管损伤，