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预防性和治疗性疫苗可保护精子健康免受鼠型衣原体引起的异常。

Prophylactic and therapeutic vaccination protects sperm health from Chlamydia muridarum-induced abnormalities.

机构信息

Queensland University of Technology, School of Biomedical Sciences and Centre for Immunology and Infection Control, Faculty of Health, Herston, QLD, Australia.

Queensland University of Technology, Central Analytical Research Facility, Brisbane, QLD, Australia.

出版信息

Biol Reprod. 2023 May 10;108(5):758-777. doi: 10.1093/biolre/ioad021.

Abstract

Chlamydia is the most common bacterial sexually transmitted infection worldwide and it is widely acknowledged that controlling the rampant community transmission of this infection requires vaccine development. In this study, for the first time, we elucidate the long-term response to male mouse chlamydial vaccination with chlamydial major outer membrane protein (MOMP) and ISCOMATRIX (IMX) both prophylactically and in a novel therapeutic setting. Vaccination significantly reduced and, in some cases, cleared chlamydial burden from the prostates, epididymides, and testes, which correlates with high IgG and IgA tires in tissues and serum. Important markers of sperm health and fertility were protected including sperm motility and proteins associated with fertility in men. Within splenocytes, expression of IFNγ, TNFα, IL17, IL13, IL10, and TGFβ were changed by both infection and vaccination within CD4 and CD8 T cells and regulatory T cells. Within the testicular tissue, phenotypic and concentration changes were observed in macrophages and T cells (resident and transitory). This revealed some pathogenic phenotypes associated with infection and critically that vaccination allows maintenance of testicular homeostasis, likely by preventing significant influx of CD4 T cells and promoting IL10 production. Finally, we demonstrated the testes contained immature (B220+) B cells and mature (CD138+) Chlamydia-specific plasma cells. Thus, through vaccination, we can maintain the healthy function of the testes, which is vital to protection of male fertility.

摘要

沙眼衣原体是全球最常见的细菌性性传播感染病原体,人们普遍认为,要控制这种感染的社区广泛传播,就需要开发疫苗。在这项研究中,我们首次阐明了使用沙眼衣原体主要外膜蛋白(MOMP)和 ISCOMATRIX(IMX)对雄性小鼠进行预防性和新型治疗性疫苗接种的长期反应。接种疫苗可显著降低并在某些情况下清除前列腺、附睾和睾丸中的衣原体负担,这与组织和血清中的高 IgG 和 IgA 滴度相关。包括精子活力和与男性生育力相关的蛋白在内的重要精子健康和生育力标志物得到了保护。在脾细胞中,IFNγ、TNFα、IL17、IL13、IL10 和 TGFβ 的表达在 CD4 和 CD8 T 细胞和调节性 T 细胞中均因感染和接种而改变。在睾丸组织中,观察到巨噬细胞和 T 细胞(常驻和一过性)的表型和浓度变化。这揭示了与感染相关的一些致病性表型,重要的是,疫苗接种可通过防止 CD4 T 细胞的大量涌入和促进 IL10 的产生,从而维持睾丸内稳态。最后,我们证明睾丸中含有不成熟(B220+)B 细胞和成熟(CD138+)的沙眼衣原体特异性浆细胞。因此,通过接种疫苗,我们可以维持睾丸的健康功能,这对于保护男性生育力至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/607b/10183362/9f3847aea8e2/ioad021ga1.jpg

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