Lipoteichoic acid mediated immune modulation of chronic pain

总结 在美国，前列腺炎每年占200万门诊就诊人数，其中包括1%的原发性前列腺炎患者。 护理医生慢性骨盆疼痛综合征（CPPS）的临床特征是排尿困难和疼痛， 会阴、睾丸、阴茎和耻骨上区域。CPPS占所有慢性前列腺炎的90%， 引起该综合征的因素尚不清楚。我们假设， 前列腺，特别是长期存活的临床菌株和常驻菌株，能够影响前列腺 免疫力当患有非感染性自身免疫性前列腺炎（实验性自身免疫性前列腺炎- EAP），滴注了Escherosal S。表皮，骨盆疼痛迅速改善， 前列腺中致病性免疫应答的负调节。这些结果让我们假设 那辆多表皮LTA（SELTA）诱导共刺激配体的表达以抑制效应T细胞， 激活调节性T细胞并消除肥大细胞脱粒，从而改善盆腔疼痛。我们 为此提出以下具体目标：1.确定S. 表皮2.定义TLR在SELTA介导的免疫调节中的作用。3.评估SELTA 缀合的高密度脂蛋白-金纳米颗粒作为盆腔疼痛的治疗药物。拟议的研究将提供一个 了解SELTA如何抑制骨盆疼痛的机制，并将开发新的切割-边缘 用于在人CP/CPPS中测试的治疗剂。

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.