The immune system fails to mount a protective response to Gram-positive or Gram-negative bacterial prostatitis

Abstract

Bacterial prostatitis affects 1% of men, with increased incidence in the elderly. It is defined by the frequency and urgency to urinate, localized pain, and positive bacterial cultures in expressed seminal fluids. Acute bacterial prostatitis frequently progresses to chronicity, which is marked by recurrent acute episodes interspersed with asymptomatic periods of variable duration. Up to 80% of bacterial prostatitis cases are caused by Gram-negative uropathogenic E. coli (UPEC) or Gram-positive E. faecalis. Antibiotic treatment is standard of care, however, global dissemination of antimicrobial resistant uropathogens threatens efficacy of therapy. Thus, development of non-antibiotic-based approaches to treat bacterial prostatitis is a priority. One challenge is that the immune response to infection in the prostate is incompletely understood. We used a mouse model of transurethral bacterial instillation to study the immune response to UPEC or E. faecalis prostate infection. Both uropathogens exhibited tropism for the prostate over the bladder early post-infection. UPEC infection induced greater proinflammatory cytokine expression and neutrophil and monocyte infiltration compared to E. faecalis infection. Following challenge infection, cytokine responses and myeloid cell infiltration were largely comparable to primary infection.Characteristic of memory responses, more lymphoid cells infiltrating the prostate in the second infection compared to the primary infection. Unexpectedly, however, bacterial burden in prostates challenged with either UPEC or E. faecalis was equal or greater than in primary infection, despite that an adaptive response to UPEC infection was evident in the bladder of the same animals. Thus, an immune response to primary infection is initiated, however it does not protect against reinfection. Our findings support the idea that chronic or recurrent prostatitis develops in the absence of efficacious immunity to infection. A greater understanding of the mechanisms underlying this observation may point to actionable targets for immunotherapy.