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Differential Bacterial Survival, Replication, and Apoptosis-Inducing Ability of Salmonella Serovars within Human and Murine Macrophages

机译:沙门氏菌血清在人和小鼠巨噬细胞中的差异细菌存活,复制和凋亡诱导能力。

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Salmonella serovars are associated with human diseases that range from mild gastroenteritis to host-disseminated enteric fever. Human infections by Salmonella enterica serovar Typhi can lead to typhoid fever, but this serovar does not typically cause disease in mice or other animals. In contrast, S. enterica serovar Typhimurium and S. entericaserovar Enteritidis, which are usually linked to localized gastroenteritis in humans and some animal species, elicit a systemic infection in mice. To better understand these observations, multiple strains of each of several chosen serovars of Salmonellawere tested for the ability in the nonopsonized state to enter, survive, and replicate within human macrophage cells (U937 and elutriated primary cells) compared with murine macrophage cells (J774A.1 and primary peritoneal cells); in addition, death of the infected macrophages was monitored. The serovar Typhimurium strains all demonstrated enhanced survival within J774A.1 cells and murine peritoneal macrophages, compared with the significant, almost 100-fold declines in viable counts noted for serovar Typhi strains. Viable counts for serovar Enteritidis either matched the level of serovar Typhi (J774A.1 macrophages) or were comparable to counts for serovar Typhimurium (murine peritoneal macrophages). Apoptosis was significantly higher in J774A.1 cells infected with serovar Typhimurium strain LT2 compared to serovar Typhi strain Ty2. On the other hand, serovar Typhi survived at a level up to 100-fold higher in elutriated human macrophages and 2- to 3-fold higher in U937 cells compared to the serovar Typhimurium and Enteritidis strains tested. Despite the differential multiplication of serovar Typhi during infection of U937 cells, serovar Typhi caused significantly less apoptosis than infections with serovar Typhimurium. These observations indicate variability in intramacrophage survival and host cytotoxicity among the various serovars and are the first to show differences in the apoptotic response of distinctSalmonella serovars residing in human macrophage cells. These studies suggest that nonopsonized serovar Typhimurium enters, multiplies within, and causes considerable, acute death of macrophages, leading to a highly virulent infection in mice (resulting in death within 14 days). In striking contrast, nonopsonized serovar Typhi survives silently and chronically within human macrophages, causing little cell death, which allows for intrahost dissemination and typhoid fever (low host mortality). The type of disease associated with any particular serovar of Salmonellais linked to the ability of that serovar both to persist within and to elicit damage in a specific host's macrophage cells.
机译:沙门氏菌血清与人类疾病有关,从轻度胃肠炎到宿主传播性肠热。伤寒鼠伤寒沙门氏菌引起的人类感染可导致伤寒,但这种血清通常不会引起小鼠或其他动物的疾病。相反,通常与人和某些动物的局部胃肠炎有关的肠炎链球菌鼠伤寒沙门氏菌和肠炎沙门氏菌肠炎沙门氏菌在小鼠中引起全身感染。为了更好地理解这些观察结果,与鼠类巨噬细胞(J774A)相比,测试了沙门氏菌的几种选择的血清型中的每一种的多种菌株在非调理状态下进入人巨噬细胞(U937和淘洗的原代细胞),在其中存活和复制的能力。 1和原代腹膜细胞);另外,监测了感染的巨噬细胞的死亡。鼠伤寒沙门氏菌菌株均显示出J774A.1细胞和鼠腹膜巨噬细胞的存活率提高,而鼠伤寒沙门氏菌菌株的存活数则下降了近100倍。肠炎血清的活计数与血清鼠伤寒(J774A.1巨噬细胞)水平相匹配,或与鼠伤寒鼠(腹膜巨噬细胞)的计数相当。与鼠伤寒沙门氏菌Ty2相比,感染鼠伤寒沙门氏菌LT2的J774A.1细胞的凋亡明显更高。另一方面,与测试的鼠伤寒沙门氏菌和肠炎沙门氏菌菌株相比,鼠伤寒沙门氏菌在淘洗的人类巨噬细胞中存活的水平高100倍,在U937细胞中存活2-3倍。尽管在感染U937细胞过程中血清型伤寒的繁殖不同,但血清型伤寒引起的细胞凋亡明显少于血清型伤寒。这些观察结果表明各种血清型之间巨噬细胞内存活的变化和宿主细胞毒性,并且是第一个显示人类巨噬细胞中独特的沙门氏菌血清型凋亡反应的差异。这些研究表明未经调理的血清型鼠伤寒沙门氏菌进入巨噬细胞,在巨噬细胞内繁殖并引起相当数量的急性死亡,导致小鼠发生高毒性感染(导致14天内死亡)。与之形成鲜明对比的是,非调理性血清型伤寒菌在人类巨噬细胞内无声且长期存活,几乎没有细胞死亡,从而允许宿主内传播和伤寒(宿主死亡率低)。与沙门氏菌的任何特定血清型有关的疾病类型与该血清型在特定宿主的巨噬细胞中持续存在并引起损伤的能力有关。

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