引用

toll样受体(TLRs)是先天免疫系统的前哨受体。TLR4检测细菌脂多糖(LPS)， TLR5检测细菌鞭毛蛋白。一种常见的人类无意义多态性，TLR5:c。1174C>T，导致无功能TLR5蛋白。携带这种变异的个体患类鼻疽病的死亡率降低，类鼻疽病是由鞭毛革兰氏阴性杆菌假鼻疽伯克霍氏菌引起的感染。尽管TLR5携带者鞭毛蛋白依赖的信号通路受损。1174C>T已经确定，本研究验证了TLR5:c的功能作用假说。1174C>T是鞭毛蛋白无关的，涉及LPS-TLR4通路。全血来自两个独立队列的个体TLR5基因分型:c。1174C>T用野生型或鞭毛B. pseudomallei或纯化的细菌基序进行刺激，然后测量血浆细胞因子。来自携带TLR5的个体的血液:c。1174C>T variant produced less IL-6 and IL-10 in response to an aflagellated B. pseudomallei mutant and less IL-8 in response to purified B. pseudomallei LPS than blood from individuals without the variant. TLR5 expression in THP1 cells was silenced using siRNA; these cells were stimulated with LPS before cytokine levels in cell supernatants were quantified by ELISA. In these cells following LPS stimulation, silencing of TLR5 with siRNA reduced both TNF- and IL-8 levels. These effects were not explained by differences in TLR4 mRNA expression or NF-B or IRF activation. The effects of the common nonsense TLR5:c.1174C>T polymorphism on the host inflammatory response to B. pseudomallei may not be restricted to flagellin-driven pathways. Moreover, TLR5 may modulate TLR4-dependent cytokine production. While these results may have broader implications for the role of TLR5 in the innate immune response in melioidosis and other conditions, further studies of the mechanisms underlying these observations are required.