Toll-Like Receptor 2 Agonist Pam3CSK4 Alleviates the Pathology of Leptospirosis in Hamster
Toll-Like Receptor 2 Agonist Pam3CSK4 Alleviates the Pathology of Leptospirosis in Hamster
复制标题
Toll 样受体 2 激动剂 Pam3CSK4 可减轻仓鼠钩端螺旋体病的病理。
DOI：
10.1128/iai.00708-16
复制
发表时间：
2016-12-01
影响因子：
3.1
通讯作者：
Cao, Yongguo
中科院分区：
文献类型：
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作者：
Zhang, Wenlong;Zhang, Naisheng;Cao, Yongguo
钩端螺旋体病是由致病性螺旋体引起的一种全球性的人畜共患疾病。钩端螺旋体病的详细发病机制至今仍不清楚，这限制了钩端螺旋体病的理想治疗。在这项研究中，我们分析了Toll样受体2（TLR 2）和TLR 4在抗性小鼠和易感仓鼠感染问号血清型秋季钩端螺旋体后的靶器官中的表达。小鼠器官中的TLR 2而非TLR 4转录物与仓鼠器官中的延迟诱导和过表达形成对比。将钩端螺旋体和TLR 2激动剂Pam 3CSK 4共注射到仓鼠体内，提高了它们的存活率，减轻了组织损伤，并降低了靶器官中钩端螺旋体的丰度。与钩体注射组相比，钩体和Pam 3CSK 4共同注射组的仓鼠组织中白细胞介素-10（IL-10）的产生增加。类似地，TLR 2缺陷小鼠中的IL-10水平低于野生型小鼠。在感染的野生型小鼠和共同注射钩端螺旋体和Pam 3CSK 4的仓鼠中发现了高比例的IL-10/肿瘤坏死因子α（TNF-α）水平。此外，TLR 2依赖性IL-10的表达检测在腹腔巨噬细胞感染钩端螺旋体。我们的数据表明，共同注射钩端螺旋体和Pam 3CSK 4的仓鼠钩端螺旋体病的病理学，这种效果可能是由于TLR 2依赖性IL-10的表达增强。
Leptospirosis, caused by pathogenic spirochetes, is a zoonotic disease of global importance. The detailed pathogenesis of leptospirosis is still unclear, which limits the ideal treatment of leptospirosis. In this study, we analyzed the expression of Toll-like receptor 2 (TLR2) and TLR4 in target organs of both resistant mice and susceptible hamsters after Leptospira interrogans serovar Autumnalis infection. TLR2 but not TLR4 transcripts in mouse organs contrasted with delayed induction and overexpression in hamster organs. Coinjection of leptospires and the TLR2 agonist Pam3CSK4 into hamsters improved their survival rate, alleviated tissue injury, and decreased the abundance of leptospires in target organs. The production of interleukin-10 (IL-10) from tissues was enhanced in hamsters of the group coinjected with leptospires and Pam3CSK4 compared with the leptospira-injected group. Similarly, IL-10 levels in TLR2-deficient mice were lower than those in wild-type mice. A high ratio of IL-10/tumor necrosis factor alpha (TNF-alpha) levels was found in both infected wild-type mice and hamsters coinjected with leptospires and Pam3CSK4. Moreover, TLR2-dependent IL-10 expression was detected in peritoneal macrophages after leptospira infection. Our data demonstrate that coinjection of leptospires and Pam3CSK4 alleviates the pathology of leptospirosis in hamsters; this effect may result from the enhanced expression of TLR2-dependent IL-10.