BACKGROUND Toll-like receptor 2 (TLR2) plays a critical role in mediating inflammatory/immune responses against bacterial pathogens in lung. Streptococcus pneumoniae (S. pneumoniae) and nontypeable Haemophilus influenzae (NTHi) were previously reported to synergize with each other to induce inflammatory responses. Despite the relatively known intracellular signaling pathways involved in the synergistic induction of inflammation, it is still unclear if both bacterial pathogens also synergistically induce expression of surface TLR2. RESULTS Here we provide direct evidence that S. pneumoniae synergizes with NTHi to upregulate TLR2 expression in lung and middle ear of the mice. Pneumolysin (PLY) appears to be the major virulence factor involved in this synergism. Moreover, S. pneumoniae PLY induces TLR2 expression via a TLR4-MyD88-NF-kappaB-dependent signaling pathway. Interestingly, tumor suppressor CYLD acts as a negative regulator of S. pneumoniae-induced TLR2 up-regulation via negative-crosstalk with NF-kappaB signaling. CONCLUSION Our study thus provides novel insights into the regulation of TLR2 expression in mixed bacterial infections.

中文翻译：

---

肺炎链球菌与不可分型流感嗜血杆菌协同作用，通过上调 TLR2 诱导炎症。

背景 Toll 样受体 2 (TLR2) 在介导针对肺部细菌病原体的炎症/免疫反应中起关键作用。先前有报道称肺炎链球菌（肺炎链球菌）和不可分型流感嗜血杆菌 (NTHi) 相互协同以诱导炎症反应。尽管相对已知的细胞内信号通路参与炎症的协同诱导，但两种细菌病原体是否也协同诱导表面 TLR2 的表达仍不清楚。结果在此我们提供了直接证据，证明肺炎链球菌与 NTHi 协同上调小鼠肺和中耳中的 TLR2 表达。肺炎球菌溶血素 (PLY) 似乎是参与这种协同作用的主要毒力因子。此外，S。肺炎链球菌 PLY 通过 TLR4-MyD88-NF-kappaB 依赖性信号通路诱导 TLR2 表达。有趣的是，肿瘤抑制因子 CYLD 通过与 NF-kappaB 信号传导的负串扰，充当肺炎链球菌诱导的 TLR2 上调的负调节器。结论因此，我们的研究为混合细菌感染中 TLR2 表达的调节提供了新的见解。