Gyorke Clare E, Kollipara Avinash, Allen John, Zhang Yugen, Ezzell J Ashley, Darville Toni, Montgomery Stephanie A, Nagarajan Uma M
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
J Immunol. 2020 Dec 1;205(11):3037-3049. doi: 10.4049/jimmunol.2000600. Epub 2020 Oct 21.
infection of the female genital tract can lead to irreversible fallopian tube scarring. In the mouse model of genital infection using 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. mice infected with 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 oviduct during peak days of infection, levels of IL-1β, IL-6, CSF3, and CXCL2 were reduced in oviduct lysates. During infection, 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.
女性生殖道感染可导致输卵管不可逆的瘢痕形成。在使用的生殖器感染小鼠模型中，IL-1R信号传导在输卵管组织损伤中起关键作用。在本研究中，我们调查了与IL-1R结合的两种促炎细胞因子之一IL-1α的病理作用。感染的小鼠宫颈感染清除率与野生型（WT）小鼠相同，但在终点时输卵管损伤和纤维化得到显著保护。IL-1α对输卵管病理的影响比在IL-1β缺陷小鼠中观察到的更为显著。虽然在感染高峰期WT小鼠和感染小鼠的输卵管中衣原体负荷相似，但感染小鼠输卵管裂解物中IL-1β、IL-6、CSF3和CXCL2的水平降低。在感染期间，感染小鼠的输卵管和子宫角中性粒细胞浸润减少，并且在感染消退后这种减少仍持续存在。在原发性或继发性衣原体感染期间，IL-1α的缺失不会损害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而表达，并且在感染清除后仍持续低水平表达。WT小鼠中通过抗体介导的IL-1α耗竭可预防感染诱导的输卵管损伤，进一步支持IL-1α在输卵管病理中的关键作用。
