Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3083-8. doi: 10.1073/pnas.1112729109. Epub 2012 Feb 1.
Disease progression of primary pneumonic plague is biphasic, consisting of a preinflammatory and a proinflammatory phase. During the long preinflammatory phase, bacteria replicate to high levels, seemingly uninhibited by normal pulmonary defenses. In a coinfection model of pneumonic plague, it appears that Yersinia pestis quickly creates a localized, dominant anti-inflammatory state that allows for the survival and rapid growth of both itself and normally avirulent organisms. Yersinia pseudotuberculosis, the relatively recent progenitor of Y. pestis, shows no similar trans-complementation effect, which is unprecedented among other respiratory pathogens. We demonstrate that the effectors secreted by the Ysc type III secretion system are necessary but not sufficient to mediate this apparent immunosuppression. Even an unbiased negative selection screen using a vast pool of Y. pestis mutants revealed no selection against any known virulence genes, demonstrating the transformation of the lung from a highly restrictive to a generally permissive environment during the preinflammatory phase of pneumonic plague.
原发性肺鼠疫的病程呈双相性，包括炎症前期和炎症期。在漫长的炎症前期，细菌大量繁殖，似乎不受正常肺部防御机制的抑制。在肺鼠疫的合并感染模型中，似乎鼠疫耶尔森菌迅速产生了局部的、优势的抗炎状态，使自身和通常无毒性的生物体得以存活和快速生长。鼠疫耶尔森菌的相对近期祖先是假结核耶尔森菌，它没有表现出类似的转互补效应，这在其他呼吸道病原体中是前所未有的。我们证明，由 Ysc 型 III 型分泌系统分泌的效应物是介导这种明显免疫抑制所必需的，但不是充分条件。甚至使用庞大的鼠疫耶尔森菌突变体库进行的无偏见负选择筛选也没有针对任何已知毒力基因进行选择，这表明在肺鼠疫的炎症前期，肺部从高度限制环境转变为普遍允许环境。
