Pathogenesis of Brucella epididymoorchitis-game of Brucella death

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.

Keywords:

• Brucella
• brucellosis
• epididymoorchitis
• macrophages
• testis

Disclosure statement

The authors declare that there are no competing interests.

Author contributions

LS and ZD developed the concept of text and figures. JY, SL and LW performed the literature search and wrote the text of the manuscript. LB and LW finalised writing the paper and made the manuscript revisions.

Additional information

Funding

This research is funded by the following projects: Natural Science Foundation of Inner Mongolia [2020MS08046]; The Major Science Foundation of Affiliated Hospital of Inner Mongolia Medical University; Natural Science Foundation of Inner Mongolia Autonomous Region [No. 2020MS08046, 2018LH08032 and 2019MS08110); Inner Mongolia Autonomous Region “Prairie excellence” Project. The Special Funds for the Local Science and Technology Development of the Central Government [1280697693076717568], Inner Mongolia Autonomous Region Science and Technology Plan Project [1261196311571464192], "Western Light" Scholar Program of Chinese Academy of Sciences.