Department of Molecular Biology and Microbiology, Tufts University, Boston MA 02111, USA.
Cell Microbiol. 2010 Aug;12(8):1064-82. doi: 10.1111/j.1462-5822.2010.01451.x. Epub 2010 Feb 9.
Type III secretion systems deliver effector proteins from Gram-negative bacterial pathogens into host cells, where they disarm host defences, allowing the pathogens to establish infection. Although Yersinia pseudotuberculosis delivers its effector proteins, called Yops, into numerous cell types grown in culture, we show that during infection Y. pseudotuberculosis selectively targets Yops to professional phagocytes in Peyer's patches, mesenteric lymph nodes and spleen, although it colocalizes with B and T cells as well as professional phagocytes. Strikingly, in the absence of neutrophils, the number of cells with translocated Yops was significantly reduced although the bacterial loads were similar, indicating that Y. pseudotuberculosis did not arbitrarily deliver Yops to the available cells. Using isolated splenocytes, selective binding and selective targeting to professional phagocytes when bacteria were limiting was also observed, indicating that tissue architecture was not required for the tropism for professional phagocytes. In isolated splenocytes, YadA and Invasin increased the number of all cells types with translocated Yops, but professional phagocytes were still preferentially translocated with Yops in the absence of these adhesins. Together these results indicate that Y. pseudotuberculosis discriminates among cells it encounters during infection and selectively delivers Yops to phagocytes while refraining from translocation to other cell types.
III 型分泌系统将效应蛋白从革兰氏阴性细菌病原体输送到宿主细胞中,在那里它们破坏宿主防御,使病原体能够建立感染。虽然假结核耶尔森氏菌将其效应蛋白(称为 Yops)输送到培养的多种细胞类型中,但我们表明,在感染过程中,假结核耶尔森氏菌选择性地将 Yops 靶向 Peyer 斑、肠系膜淋巴结和脾脏中的专业吞噬细胞,尽管它也与 B 细胞和 T 细胞以及专业吞噬细胞共定位。引人注目的是,在没有中性粒细胞的情况下,尽管细菌负荷相似,但具有易位 Yops 的细胞数量明显减少,这表明假结核耶尔森氏菌并没有任意将 Yops 输送到可用的细胞中。使用分离的脾细胞,当细菌数量有限时,还观察到选择性结合和选择性靶向专业吞噬细胞,表明组织结构不是对专业吞噬细胞的嗜性所必需的。在分离的脾细胞中,YadA 和 Invasin 增加了所有细胞类型中具有易位 Yops 的数量,但在没有这些粘附素的情况下,专业吞噬细胞仍然优先易位 Yops。这些结果表明,假结核耶尔森氏菌在感染过程中遇到的细胞之间进行区分,并选择性地将 Yops 输送到吞噬细胞,同时避免向其他细胞类型易位。