Department of Pediatrics, University of Washington, Seattle, WA, USA.
Cell Microbiol. 2009 May;11(5):755-68. doi: 10.1111/j.1462-5822.2009.01288.x. Epub 2009 Jan 15.
Pseudomonas aeruginosa is an opportunistic human pathogen that can cause serious infection in those with deficient or impaired phagocytes. We have developed the optically transparent and genetically tractable zebrafish embryo as a model for systemic P. aeruginosa infection. Despite lacking adaptive immunity at this developmental stage, zebrafish embryos were highly resistant to P. aeruginosa infection, but as in humans, phagocyte depletion dramatically increased their susceptibility. The virulence of an attenuated P. aeruginosa strain lacking a functional Type III secretion system was restored upon phagocyte depletion, suggesting that this system influences virulence through its effects on phagocytes. Intravital imaging revealed bacterial interactions with multiple blood cell types. Neutrophils and macrophages rapidly phagocytosed and killed P. aeruginosa, suggesting that both cell types play a role in protection against infection. Intravascular aggregation of erythrocytes and other blood cells with resultant circulatory blockage was observed immediately upon infection, which may be relevant to the pathogenesis of thrombotic complications of human P. aeruginosa infections. The real-time visualization capabilities and genetic tractability of the zebrafish infection model should enable elucidation of molecular and cellular details of P. aeruginosa pathogenesis in conditions associated with neutropenia or impaired phagocyte function.
铜绿假单胞菌是一种机会性人类病原体，可导致吞噬细胞功能缺陷或受损的人群发生严重感染。我们已经开发出光学透明且遗传可操作的斑马鱼胚胎作为全身性铜绿假单胞菌感染的模型。尽管在这个发育阶段斑马鱼胚胎缺乏适应性免疫，但它们对铜绿假单胞菌感染具有高度抗性，但与人类一样，吞噬细胞耗竭会极大地增加它们的易感性。吞噬细胞耗竭后，一种缺失功能性 III 型分泌系统的减毒铜绿假单胞菌菌株的毒力得到恢复，表明该系统通过对吞噬细胞的影响来影响毒力。活体成像显示了细菌与多种血细胞类型的相互作用。中性粒细胞和巨噬细胞迅速吞噬并杀死铜绿假单胞菌，表明这两种细胞类型都在抗感染中发挥作用。感染后立即观察到红细胞和其他血细胞的血管内聚集以及由此导致的循环阻塞，这可能与人类铜绿假单胞菌感染的血栓并发症的发病机制有关。斑马鱼感染模型的实时可视化能力和遗传可操作性应能阐明与中性粒细胞减少或吞噬细胞功能受损相关的条件下铜绿假单胞菌发病机制的分子和细胞细节。
