A Dual Role for the Plasminogen Activator Protease During the Preinflammatory Phase of Primary Pneumonic Plague
A Dual Role for the Plasminogen Activator Protease During the Preinflammatory Phase of Primary Pneumonic Plague
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DOI：
10.1093/infdis/jiaa094
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发表时间：
2020-08-01
影响因子：
6.4
通讯作者：
Pechous, Roger D.
中科院分区：
文献类型：
--
作者：
Banerjee, Srijon K.;Crane, Samantha D.;Pechous, Roger D.
吸入后早期，在没有疾病症状或明显炎症反应的情况下，鼠疫耶尔森氏菌会在呼吸道内大量复制，从而导致原发肺鼠疫。纤溶酶原激活物蛋白水解酶(Pla)是一种重要的鼠疫杆菌毒力因子，通过一种未知的机制对早期细菌在肺内的生长起重要作用。在这篇文章中，我们定义了Pla在肺部感染初期的双重作用。我们证明Pla作为一种不依赖于其蛋白分解功能的粘附素来抑制早期中性粒细胞进入肺内，并且Pla的酶活性有助于细菌对中性粒细胞介导的细菌杀伤的抵抗力。我们的结果表明，鼠疫杆菌感染肺部的命运是在感染过程中很早就决定的，Pla起着双重作用，使天平向有利于病原体的方向倾斜。
Early after inhalation, Yersinia pestis replicates to high numbers in the airways in the absence of disease symptoms or notable inflammatory responses to cause primary pneumonic plague. The plasminogen activator protease (Pla) is a critical Y. pestis virulence factor that is important for early bacterial growth in the lung via an unknown mechanism. In this article, we define a dual role for Pla in the initial stages of pulmonary infection. We show that Pla functions as an adhesin independent of its proteolytic function to suppress early neutrophil influx into the lungs, and that Pla enzymatic activity contributes to bacterial resistance to neutrophil-mediated bacterial killing. Our results suggest that the fate of Y. pestis infection of the lung is decided extremely early during infection and that Pla plays a dual role to tilt the balance in favor of the pathogen.