黄体酮通过激活宫颈驻留巨噬细胞与中性粒细胞之间的串联作用,促进依赖 Cxcl2 的阴道中性粒细胞杀伤作用。

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Carla Gómez-Oro, Maria C Latorre, Patricia Arribas-Poza, Alexandra Ibáñez-Escribano, Katia R Baca-Cornejo, Jorge Gallego-Valle, Natalia López-Escobar, Mabel Mondéjar-Palencia, Marjorie Pion, Luis A López-Fernández, Enrique Mercader, Federico Pérez-Milán, Miguel Relloso
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引用次数: 0

摘要

育龄妇女的阴道感染是一个对社会经济有重大影响的临床难题。人们对早期病原体入侵时粘膜免疫失效,导致病原体生长和繁殖的认识还远远不够。作为正常修复、微生物群调节或免疫监视的一部分,中性粒细胞按照昼夜节律浸润大多数组织,并在感染后变得更多。中性粒细胞负责维持阴道免疫。在阴道中,中性粒细胞持续高水平浸润,但在排卵期间,它们会退缩以避免精子受损,并允许生殖。在这里,我们发现在排卵后,孕酮通过上调卵黄囊和胎儿早期器官(Folr2+(叶酸受体 2))巨噬细胞 Cxcl2 的表达,以 Tnfa-单核细胞源性巨噬细胞(Cx3cr1hi MHCIIhi)介导的方式,促进常驻阴道巨噬细胞-中性粒细胞的串联,从而激活中性粒细胞消除性传播和机会性微生物的能力。事实上,黄体酮在协调共生微生物群、精子和病原体威胁之间的平衡方面起着至关重要的作用:因为黄体酮不仅能促进中性粒细胞的大量繁殖,还能增加中性粒细胞的愤怒,从而在排卵后恢复免疫力,挫败性交后的病原体入侵。因此,适度的孕酮失调可能会导致中性粒细胞反应不理想,从而导致粘膜防御不足和反复感染。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Progesterone promotes CXCl2-dependent vaginal neutrophil killing by activating cervical resident macrophage-neutrophil crosstalk.

Vaginal infections in women of reproductive age represent a clinical dilemma with significant socioeconomic implications. The current understanding of mucosal immunity failure during early pathogenic invasions that allows the pathogen to grow and thrive is far from complete. Neutrophils infiltrate most tissues following circadian patterns as part of normal repair, regulation of microbiota, or immune surveillance and become more numerous after infection. Neutrophils are responsible for maintaining vaginal immunity. Specific to the vagina, neutrophils continuously infiltrate at high levels, although during ovulation, they retreat to avoid sperm damage and permit reproduction. Here we show that, after ovulation, progesterone promotes resident vaginal macrophage-neutrophil crosstalk by upregulating Yolk sac early fetal organs (FOLR2+) macrophage CXCl2 expression, in a TNFA-patrolling monocyte-derived macrophage-mediated (CX3CR1hiMHCIIhi-mediated) manner, to activate the neutrophils' capacity to eliminate sex-transmitted and opportunistic microorganisms. Indeed, progesterone plays an essential role in conciliating the balance between the commensal microbiota, sperm, and the threat of pathogens because progesterone not only promotes a flurry of neutrophils but also increases neutrophilic fury to restore immunity after ovulation to thwart pathogenic invasion after intercourse. Therefore, modest progesterone dysregulations could lead to a suboptimal neutrophilic response, resulting in insufficient mucosal defense and recurrent unresolved infections.

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来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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