Lipoteichoic acid mediated immune modulation of chronic pain

总结

Summary Prostatitis accounts for 2 million outpatient visits per year in the United States, including 1% of those to primary care physicians. Chronic pelvic pain syndrome (CPPS) is clinically characterized by dysuria and pain in the perineum, testes, penis and suprapubic region. CPPS accounts for 90% of all chronic prostatitis but the initiating factors that establish the syndrome are unknown. We hypothesized that bacterial isolates from the prostate, particularly long--‐lived clinical strains and resident commensals, are capable of influencing prostate immunity. When mice with non--‐infectious autoimmune prostatitis (Experimental autoimmune prostatitis - EAP), were instilled with the commensal S. epidermidis, there was a rapid amelioration of pelvic pain and a negative modulation of the pathogenic immune response in the prostate. These results lead us to hypothesize that S. epidermidis LTA (SELTA) induces expression of co--‐stimulatory ligands to inhibit effector T cells, activate regulatory T cells and abrogate mast cell degranulation, resulting in the amelioration of pelvic pain. We therefore propose the following specific aims: 1. Identifying the mechanism of pain attenuation mediated by S. epidermidis LTA. 2. Defining the role of TLR’s in SELTA--‐mediated immune modulation. 3. Evaluating SELTA conjugatedHDL--‐goldnanoparticles as a therapeutic for pelvic pain. The proposed studies will provide a mechanistic understanding of how SELTA inhibits pelvic pain and will develop novel cutting--‐edge therapeutics for testing in human CP/CPPS.