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Immune response induced by Salmonella typhimurium defective in ppGpp synthesis

机译：ppGpp合成中鼠伤寒沙门氏菌引起的免疫应答

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摘要

Systemic infection by Salmonella typhimurium requires coordinated expression of virulence genes found primarily in Salmonella Pathogenecity Islands (SPIs). We have previously reported that the intracellular signal that induces these virulence genes is a stringent signal molecule, ppGpp [Song et al. J Biol Chem 2003;279:34183]. In this study, we found that relA and spoT double mutant Salmonella (DeltappGpp strain), which is defective in ppGpp synthesis, was virtually avirulent in BALB/c mice. Subsequently, the live vaccine potential of the avirulent DeltappGpp Salmonella strain was determined. A single immunization with live DeltappGpp Salmonella efficiently protected mice from challenge with wild-type Salmonella at a dose 10(6)-fold above the LD50 30 days after immunization. Various assays revealed that immunization of mice with the DeltappGpp strain elicited both systemic and mucosal antibody responses, in addition to cell-mediated immunity.
机译：鼠伤寒沙门氏菌的全身感染需要协同表达主要在沙门氏菌病原体岛（SPIs）中发现的毒力基因。先前我们已经报道过，诱导这些毒力基因的细胞内信号是严格的信号分子，ppGpp [Song等。生物化学杂志2003; 279：34183]。在这项研究中，我们发现在ppGpp合成中存在缺陷的relA和spoT双突变沙门氏菌（DeltappGpp株）在BALB / c小鼠中几乎无毒。随后，确定无毒的DeltappGpp沙门氏菌菌株的活疫苗潜力。活的DeltappGpp沙门氏菌的单次免疫有效地保护了小鼠，使其免受野生型沙门氏菌的攻击，该剂量比免疫后30天的LD50高10（6）倍。各种测定表明，除了细胞介导的免疫力之外，用DeltappGpp株对小鼠进行免疫还引起全身和粘膜抗体应答。

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