Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Infect Immun. 2011 Dec;79(12):4984-9. doi: 10.1128/IAI.05307-11. Epub 2011 Oct 3.
The ability of Yersinia pestis to forestall the mammalian innate immune response is a fundamental aspect of plague pathogenesis. In this study, we examined the effect of Ail, a 17-kDa outer membrane protein that protects Y. pestis against complement-mediated lysis, on bubonic plague pathogenesis in mice and rats. The Y. pestis ail mutant was attenuated for virulence in both rodent models. The attenuation was greater in rats than in mice, which correlates with the ability of normal rat serum, but not mouse serum, to kill ail-negative Y. pestis in vitro. Intradermal infection with the ail mutant resulted in an atypical, subacute form of bubonic plague associated with extensive recruitment of polymorphonuclear leukocytes (PMN or neutrophils) to the site of infection in the draining lymph node and the formation of large purulent abscesses that contained the bacteria. Systemic spread and mortality were greatly attenuated, however, and a productive adaptive immune response was generated after high-dose challenge, as evidenced by high serum antibody levels against Y. pestis F1 antigen. The Y. pestis Ail protein is an important bubonic plague virulence factor that inhibits the innate immune response, in particular the recruitment of a protective PMN response to the infected lymph node.
鼠疫耶尔森氏菌阻止哺乳动物固有免疫反应的能力是鼠疫发病机制的一个基本方面。在这项研究中，我们研究了 Ail（一种 17kDa 的外膜蛋白，可保护鼠疫耶尔森氏菌免受补体介导的裂解）对小鼠和大鼠败血性鼠疫发病机制的影响。Y. pestis ail 突变体在这两种啮齿动物模型中的毒力都减弱了。在大鼠中的衰减程度大于在小鼠中，这与正常大鼠血清但不是小鼠血清在体外杀死 ail 阴性 Y. pestis 的能力相关。皮内感染 ail 突变体导致典型的亚急性败血性鼠疫，与感染部位引流淋巴结中多形核白细胞（PMN 或中性粒细胞）的广泛募集以及形成含有细菌的大脓性脓肿有关。然而，全身性传播和死亡率大大降低，并且在高剂量挑战后产生了有效的适应性免疫反应，这表现在针对 Y. pestis F1 抗原的高血清抗体水平上。鼠疫耶尔森氏菌 Ail 蛋白是一种重要的败血性鼠疫毒力因子，可抑制固有免疫反应，特别是对感染淋巴结中保护性 PMN 反应的募集。
