Pathogenesis of Brucella epididymoorchitis-game of Brucella death

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.HIGHLIGHTSWe 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.