Fällman M, Andersson K, Håkansson S, Magnusson K E, Stendahl O, Wolf-Watz H
Department of Medical Microbiology, Linköping University, Sweden.
Infect Immun. 1995 Aug;63(8):3117-24. doi: 10.1128/iai.63.8.3117-3124.1995.
Nonopsonized as well as immunoglobulin-G (IgG)-opsonized Yersinia pseudotuberculosis resists phagocytic uptake by the macrophage-like cell line J774 by a mechanism involving the plasmid-encoded proteins Yops. The tyrosine phosphatase YopH was of great importance for the antiphagocytic effect of the bacteria. YopH-negative mutants did not induce antiphagocytosis; instead, they were readily ingested, almost to the same extent as that of the translocation mutants YopB and YopD and the plasmid-cured strain. The bacterial determinant invasin was demonstrated to mediate phagocytosis of nonopsonized bacteria by these cells. In addition to inhibiting uptake of itself, Y. pseudotuberculosis also interfered with the phagocytic uptake of other types of prey: J774 cells that had been exposed to virulent Y. pseudotuberculosis exhibited a reduced capacity to ingest IgG-opsonized yeast particles. This effect was impaired when the bacterium-phagocyte interaction occurred in the presence of gentamicin, indicating a requirement for in situ bacterial protein synthesis. The Yersinia-mediated antiphagocytic effect on J774 cells was reversible: after 18 h in the presence of gentamicin, the phagocytic capacity of Yersinia-exposed J774 cells was completely restored. Inhibition of the uptake of IgG-opsonized yeast particles was dependent on the Yops in a manner similar to that seen for blockage of Yersinia phagocytosis. This similarity suggests that the pathogen affected a general phagocytic mechanism. Despite a marked reduction in the capacity to ingest IgG-opsonized yeast particles, no effect was observed on the binding of the prey. Taken together, these results demonstrate that Yop-mediated antiphagocytosis by Y. pseudotuberculosis affects regulatory functions downstream of the phagocytic receptor and thereby extends to other types of phagocytosis.
未被调理素化以及免疫球蛋白G（IgG）调理素化的假结核耶尔森菌通过一种涉及质粒编码蛋白Yops的机制，抵抗巨噬细胞样细胞系J774的吞噬摄取。酪氨酸磷酸酶YopH对细菌的抗吞噬作用至关重要。YopH阴性突变体不会诱导抗吞噬作用；相反，它们很容易被摄取，摄取程度几乎与转位突变体YopB和YopD以及质粒消除菌株相同。细菌决定簇侵袭素被证明介导这些细胞对未被调理素化细菌的吞噬作用。除了抑制自身的摄取外，假结核耶尔森菌还干扰了其他类型猎物的吞噬摄取：暴露于有毒假结核耶尔森菌的J774细胞摄取IgG调理素化酵母颗粒的能力降低。当细菌与吞噬细胞的相互作用在庆大霉素存在的情况下发生时，这种效应会减弱，这表明需要原位细菌蛋白质合成。耶尔森菌介导的对J774细胞的抗吞噬作用是可逆的：在庆大霉素存在下18小时后，暴露于耶尔森菌的J774细胞的吞噬能力完全恢复。对IgG调理素化酵母颗粒摄取的抑制以类似于阻断耶尔森菌吞噬作用的方式依赖于Yops。这种相似性表明病原体影响了一种普遍的吞噬机制。尽管摄取IgG调理素化酵母颗粒的能力显著降低，但未观察到对猎物结合的影响。综上所述，这些结果表明假结核耶尔森菌由Yop介导的抗吞噬作用影响吞噬受体下游的调节功能，从而扩展到其他类型的吞噬作用。
