Abstract

Brucellosis is a worldwide zoonotic disease caused by Brucella spp. Human infection often results from direct contact with tissues from infected animals or by consumption of undercooked meat and unpasteurised dairy products, causing serious economic losses and public health problems. The male genitourinary system is a common involved system in patients with brucellosis. Among them, unilateral orchitis and epididymitis are the most common. Although the clinical and imaging aspect of orchi-epididymitis caused by brucellosis have been widely described, the cellular and molecular mechanisms involved in the damage and the immune response in testis and epididymis have not been fully elucidated. In this review, we first summarised the clinical characteristics of Brucella epididymo-orchitis and the composition of testicular and epididymal immune system. Secondly, with regard to the mechanism of Brucella epididymoorchitis, we mainly discussed the process of Brucella invading testis and epididymis in temporal and spatial order, including i) Brucella evades innate immune recognition of testicular PRRs；ii) Brucella overcomes the immune storm triggered by the invasion of testis through bacterial lipoproteins and virulence factors, and changes the secretion mode of cytokines; iii) Brucella breaks through the blood-testis barrier with the help of macrophages, and inflammatory cytokines promote the oxidative stress of Sertoli cells, damaging the integrity of BTB; iv) Brucella inhibits apoptosis of testicular phagocytes. Finally, we revealed the structure and sequence of testis invaded by Brucella at the tissue level. This review will enable us to better understand the pathogenesis of orchi-epididymitis caused by brucellosis and shed light on the development of new treatment strategies for the treatment of brucellosis and the prevention of transition to chronic form. Facing the testicle with immunity privilege, Brucella is like Bruce Lee in the movie Game of Death, winning is survival while losing is death.

• HIGHLIGHTS

• We summarized the clinical features and pathological changes of Brucellaepididymoorchitis.

• Our research reveals the pathogenesis of Brucella epididymoorchitis, which mainly includes the subversion of testicular immune privilege by Brucella and a series of destructive reactions derived from it.

• As a basic framework and valuable resource, this study can promote the exploration of the pathogenesis of Brucella and provide reference for determining new therapeutic targets for brucellosis in the future.

摘要

布鲁氏菌病是一种由布鲁氏菌属引起的世界性人畜共患病。人类感染通常是由直接接触受感染动物的组织或食用未煮熟的肉类和未经高温消毒的乳制品引起的，造成严重的经济损失和公共卫生问题。男性泌尿生殖系统是布鲁氏菌病患者常见的累及系统。其中以单侧睾丸炎和附睾炎最为常见。尽管布鲁氏菌病引起的睾丸附睾炎的临床和影像学方面已被广泛描述，但涉及睾丸和附睾损伤和免疫反应的细胞和分子机制尚未完全阐明。在这篇综述中，我们首先总结了布鲁氏菌的临床特征附睾-睾丸炎和睾丸和附睾免疫系统的组成。其次，关于布氏杆菌附睾炎的发病机制，我们主要讨论了布氏杆菌在时间和空间上侵入睾丸和附睾的过程，包括i)布氏杆菌逃避睾丸PRRs的先天免疫识别；ii)布氏杆菌克服由睾丸炎引发的免疫风暴。通过细菌脂蛋白和毒力因子侵入睾丸，改变细胞因子的分泌方式；iii)布鲁氏菌在巨噬细胞的帮助下突破血睾丸屏障，炎性细胞因子促进支持细胞的氧化应激，破坏BTB的完整性；iv)布鲁氏菌抑制睾丸吞噬细胞的凋亡。最后，我们在组织水平上揭示了布鲁氏菌侵入睾丸的结构和序列。本综述将使我们能够更好地了解布鲁氏菌病引起的睾丸附睾炎的发病机制，并为布鲁氏菌病治疗和预防向慢性转变的新治疗策略的发展提供启示。面对具有免疫特权的睾丸，布鲁氏菌就像电影《死亡游戏》中的李小龙，赢就是生存，输就是死。

• 强调

• 我们总结了布氏杆菌附睾炎的临床特点和病理变化。

• 我们的研究揭示了布氏杆菌附睾炎的发病机制，主要包括布氏杆菌对睾丸免疫特权的颠覆及其衍生的一系列破坏性反应。

• 本研究作为基础框架和宝贵资源，可促进对布鲁氏菌发病机制的探索，为今后确定布鲁氏菌病新的治疗靶点提供参考。