Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane
Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane
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DOI：
10.4049/jimmunol.166.9.5741
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发表时间：
2001-05-01
影响因子：
4.4
通讯作者：
Nauseef, WM
中科院分区：
文献类型：
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作者：
Gallois, A;Klein, JR;Nauseef, WM
鼠伤寒沙门氏菌需要由致病岛（SPI）-2编码的III型分泌系统在巨噬细胞内存活和增殖。这种生存意味着S.鼠伤寒沙门氏菌避免或耐受靶向含微生物的空泡的杀菌事件，所述杀菌事件包括吞噬体内产生活性氧（ROS）、吞噬体酸化和通过与溶酶体融合将水解酶递送至吞噬体。最近的证据表明，S。鼠伤寒沙门氏菌以SPI-2依赖性方式改变鼠巨噬细胞的ROS产生。为了深入了解S.鼠伤寒沙门氏菌抑制吞噬体内ROS的产生，我们分析了野生型（WT）或几种SPI-2突变株感染人单核细胞衍生的巨噬细胞过程中NADPH氧化酶组分的亚细胞分布。鼠伤寒。我们发现，NADPH氧化酶的膜组分，黄细胞色素B（558），被主动排除或迅速从WT感染的单核细胞衍生的巨噬细胞的吞噬体膜中去除，从而阻止NADPH氧化酶复合物的组装和吞噬体内超氧阴离子的产生。相比之下，NADPH氧化酶在含有SPI-2突变体S.鼠伤寒。S.与SPI-2突变株相比，WT S.鼠伤寒沙门氏菌阻止NADPH氧化酶在吞噬体膜上的组装代表了影响其细胞内存活的重要毒力因子。
Salmonella typhimurium requires a type III secretion system encoded by pathogenicity island (SPI)-2 to survive and proliferate within macrophages. This survival implies that S. typhimurium avoids or withstands bactericidal events targeted to the microbe-containing vacuole, which include intraphagosomal production of reactive oxygen species (ROS), phagosomal acidification, and delivery of hydrolytic enzymes to the phagosome via fusion with lysosomes. Recent evidence suggests that S. typhimurium alters ROS production by murine macrophages in an SPI-2-dependent manner. To gain insights into the mechanism by which S. typhimurium inhibits intraphagosomal ROS production, we analyzed the subcellular distribution of NADPH oxidase components during infection of human monocyte-derived macrophages by wild-type (WT) or several SPI-2 mutant strains of S. typhimurium. We found that the membrane component of the NADPH oxidase, flavocytochrome b(558), was actively excluded or rapidly removed from the phagosomal membrane of WT-infected monocyte-derived macrophages, thereby preventing assembly of the NADPH oxidase complex and intraphagosomal production of superoxide anion. In contrast, the NADPH oxidase assembled on and generated ROS in phagosomes containing SPI-2 mutant S. typhimurium. Subversion of NADPH oxidase assembly by S. typhimurium was accompanied by increased bacterial replication relative to that of SPI-2 mutant strains, suggesting that the ability of WT S. typhimurium to prevent NADPH oxidase assembly at the phagosomal membrane represents an important virulence factor influencing its intracellular survival.