Molecular Immunology Group, Department for Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Campus, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, United Kingdom.
Dev Comp Immunol. 2010 Aug;34(8):797-804. doi: 10.1016/j.dci.2010.02.008. Epub 2010 Mar 4.
Recently, it has been reported that Salmonella secrete flagellin in response to host produced lysophospholipids. However, this monomer of the bacterial flagella activates Toll-like receptor 5 (TLR5) in the innate immune system. The objective of this study was to examine the role of flagellin expression during infection of species-specific macrophages (MPhi) which either expressed or lacked TLR5. Initially, TLR5-activity was confirmed in bovine MPhi using Salmonella typhimurium derived-flagellin. Within these cells, recombinant FliC induced a potent CXCL8 response when compared to the heterogeneous (FliC/FljB) form of purified flagellin. Furthermore, neither form of flagellin induced nitrite secretion which was subsequently detected after exposing bovine MPhi to LPS in the presence of IFN-gamma. Flagellin enhanced the accumulation of Salmonella enteritidis in TLR5-positive bovine and human MPhi which was independent of adhesion in bovine MPhi. In contrast, murine MPhis which lacked TLR5 were equally susceptible to hosting S. enteritidis, with or without flagellin. However, lack of flagellin in S. typhimurium marginally inhibited bacterial accumulation in bovine MPhi, where FljB and FliC compensated for the lack of each other. This study suggests that flagellin may be inducing TLR5-dependent internalisation mechanisms in Mcapital EF, Cyrillic which vary qualitatively between different species and Salmonella serotypes.
最近有报道称，沙门氏菌会响应宿主产生的溶血磷脂而分泌鞭毛蛋白。然而，这种细菌鞭毛的单体在先天免疫系统中激活 Toll 样受体 5（TLR5）。本研究的目的是研究在感染具有特定物种的巨噬细胞（MPhi）时，鞭毛蛋白表达的作用，这些巨噬细胞表达或缺乏 TLR5。最初，使用鼠伤寒沙门氏菌衍生的鞭毛蛋白在牛巨噬细胞中证实了 TLR5 活性。在这些细胞中，与纯化的鞭毛蛋白的异质（FliC/FljB）形式相比，重组 FliC 诱导了强烈的 CXCL8 反应。此外，鞭毛蛋白既没有诱导硝酸盐分泌，也没有在 IFN-γ存在的情况下将牛巨噬细胞暴露于 LPS 后检测到硝酸盐分泌。鞭毛蛋白增强了肠沙门氏菌在 TLR5 阳性牛和人巨噬细胞中的积累，这与牛巨噬细胞中的粘附无关。相比之下，缺乏 TLR5 的鼠巨噬细胞同样容易被肠沙门氏菌感染，无论是否有鞭毛蛋白。然而，鼠伤寒沙门氏菌缺乏鞭毛蛋白会轻微抑制牛巨噬细胞中细菌的积累，而 FljB 和 FliC 可以相互补偿。这项研究表明，鞭毛蛋白可能在诱导不同物种和沙门氏菌血清型之间存在定性差异的巨噬细胞内化机制中依赖 TLR5。
