引用

人类腹泻病原菌空肠弯曲杆菌和弯曲杆菌杆菌干扰宿主先天免疫信号通过不同方式,和他们的鞭毛蛋白,FlaA和松弛,有较低的内在属性激活先天免疫受体toll样受体5 (TLR5)。我们这里有研究的假设不寻常的分泌,flagellin-like分子FlaC出现在c .空肠c .杆菌和其他Campylobacterales可能激活细胞通过与TLR5 TLR5和互动。FlaC序列显示了惊人的身份在D1域TLR5-activating鞭毛蛋白的其他细菌,如沙门氏菌,但不要nonstimulating弯曲杆菌鞭毛蛋白。我们过表达和纯化FlaC和测试其免疫刺激性人类起源和鸡的细胞上的属性。细胞治疗与高纯度FlaC导致p38激活。FlaC直接与TLR5互动。预培养与FlaC减少鸡的响应性和人类macrophage-like细胞对细菌TLR4受体激动剂脂多糖(LPS),这表明FlaC介导交叉抗性。c .空肠flaC突变体诱导增加细胞反应与野生型相比,抑制的基因互补。补充过量纯化FlaC同样减少c .空肠的细胞反应。体内,超纯FlaC管理导致减少盲肠的白介素1 (il - 1)的表达和鸡盲肠的微生物群的一个重要改变。 We propose that Campylobacter spp. have evolved a novel type of secreted immunostimulatory flagellin-like effector in order to specifically modulate host responses, for example toward other pattern recognition receptor (PRR) ligands, such as LPS. IMPORTANCE Flagellins not only are important for bacterial motility but are major bacterial proteins that can modulate host responses via Toll-like receptor 5 (TLR5) or other pattern recognition receptors. Campylobacterales colonizing the intestinal tracts of different host species harbor a gene coding for an unusual flagellin, FlaC, that is not involved in motility but is secreted and possesses a chimeric amino acid sequence composed of TLR5-activating and non-TLR5-activating flagellin sequences. Campylobacter jejuni FlaC activates cells to increase in cytokine expression in chicken and human cells, promotes cross-tolerance to TLR4 ligands, and alters chicken cecal microbiota. We propose that FlaC is a secreted effector flagellin that has specifically evolved to modulate the immune response in the intestinal tract in the presence of the resident microbiota and may contribute to bacterial persistence. The results also strengthen the role of the flagellar type III apparatus as a functional secretion system for bacterial effector proteins.