Lipoteichoic acid mediated immune modulation of chronic pain

Project: Research project

Project Details

Description

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
StatusActive
Effective start/end date8/1/167/31/21

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK108127-04)

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