Epididymitis promotes formation of tertiary lymphoid organs in the cauda epididymidis

Uropathogenic Escherichia coli is a common pathogen that affects the cauda epididymidis, causing interstitial edema, epithelial damage, leukocyte infiltration, and fibrosis. Despite antibiotic treatment, up to 20 % of patients develop abscesses in the cauda epididymidis, and 40 % experience low sperm counts. To understand the mechanisms of infertility impairment caused by epididymitis, we aimed to investigate the histopathological and immunological changes affecting the cauda epididymidis focusing on later post-acute stages of UPEC infection. Using a bacterial mouse model of acute epididymitis, we identified organized tertiary lymphoid organs (TLOs) that formed in the cauda epididymidis at 28 days post-infection. These appear as compartmentalized B- and T-cell clusters containing high endothelial venules (HEV) with evidence of an active germinal centre. Transcriptomic analysis confirmed the existence of a supportive microenvironment conducive to TLO formation and maintenance. Furthermore, TLO formation was also observed in human cauda epididymidis following chronic epididymitis, as documented by the presence of B- and T-cell clusters adjacent to HEV. Elevated concentrations of CXCL13 were measured in sera from epididymitis patients in acute and post-acute phase of disease. Our data suggest that TLOs in the cauda epididymidis harbor a functionally active germinal centre, which may impact male fertility in the long term.