Commensal bacterial modulation of the host immune response to ameliorate pain in a murine model of chronic prostatitis.
Commensal bacterial modulation of the host immune response to ameliorate pain in a murine model of chronic prostatitis.
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DOI：
10.1097/j.pain.0000000000000944
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发表时间：
2017-08
期刊：
影响因子：
7.4
通讯作者：
Thumbikat P
中科院分区：
文献类型：
--
作者：
Murphy SF;Schaeffer AJ;Done JD;Quick ML;Acar U;Thumbikat P
人类共生菌群在调节免疫反应以控制体内平衡中起着重要作用。表皮葡萄球菌是一种最常与皮肤相关的共生细菌，它在局部发挥这种作用，在炎症期间调节局部免疫反应，防止病原体（如金黄色葡萄球菌）的重复感染。虽然许多人认为前列腺是无菌的，但多项研究表明，少量革兰氏阳性细菌，如表皮葡萄球菌，可以从健康和患病男性的表达前列腺分泌物（EPS）中分离出来。慢性盆腔疼痛综合征（CPPS）是一种复杂的综合征，其症状包括疼痛和下尿路功能障碍（LUTs）。病因不明，有效治疗方法有限，但与前列腺免疫反应调节有关。CPPS可以使用小鼠实验性前列腺炎（EAP）建模，其中CD4+ve IL17A+ve t细胞已被证明在盆腔触觉异常性痛的疾病协调和发展中发挥关键作用。在这里，我们报告了从健康男性EPS中分离的一种特异性表皮葡萄球菌菌株（指定NPI（非疼痛性））经尿道注入EAP治疗的小鼠，可减少盆腔触觉异常性痛反应，并增加与EAP相关的CD4+ve IL17A+ve t细胞数量。此外，NPI的细胞壁成分脂质酸（LTA）特异性地概括了这些作用，并介导ctla4样配体PDL1和PDL2在前列腺CD11b+ve抗原呈递细胞上的表达增加。这些结果确定了共生表皮葡萄球菌NPI LTA在前列腺炎相关疼痛治疗中的新的潜在治疗作用。
The human commensal microflora plays an essential role in modulating the immune response to control homeostasis. Staphylococcus epidermidis, a commensal bacteria most commonly associated with the skin exerts such effects locally, modulating local immune responses during inflammation and preventing superinfection by pathogens such as Staphylococcus aureus. While the prostate is considered by many to be sterile, multiple investigations have shown that small numbers of gram-positive bacterial species such as S. epidermidis can be isolated from the expressed prostatic secretions (EPS) of both healthy and diseased men. Chronic pelvic pain syndrome (CPPS) is a complex syndrome with symptoms including pain and lower urinary tract dysfunction (LUTs). It has an unknown etiology and limited effective treatments but is associated with modulation of prostate immune responses. CPPS can be modeled using murine experimental prostatitis (EAP) where CD4+ve IL17A+ve T-cells have been shown to play a critical role in disease orchestration and development of pelvic tactile allodynia. Here we report that intra-urethral instillation of a specific S. epidermidis strain (designated NPI (non pain-inducing)), isolated from the EPS of a healthy human male, into EAP treated mice reduced the pelvic tactile allodynia responses and the increased CD4+ve IL17A+ve T-cell numbers associated with EAP. Furthermore, a cell wall constituent of NPI, lipotechoic acid (LTA), specifically recapitulates these effects and mediates increased expression of CTLA4-like ligands PDL1 and PDL2 on prostatic CD11b+ve antigen presenting cells. These results identify a new potential therapeutic role for commensal S. epidermidis NPI LTA in the treatment of prostatitis-associated pain.
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