Pseudomonas aeruginosa Type III secretion system interacts with phagocytes to modulate systemic infection of zebrafish embryos.
Pseudomonas aeruginosa Type III secretion system interacts with phagocytes to modulate systemic infection of zebrafish embryos.
复制标题
DOI：
10.1111/j.1462-5822.2009.01288.x
复制
发表时间：
2009-05
影响因子：
3.4
通讯作者：
Moskowitz SM
中科院分区：
文献类型：
--
作者：
Brannon MK;Davis JM;Mathias JR;Hall CJ;Emerson JC;Crosier PS;Huttenlocher A;Ramakrishnan L;Moskowitz SM
铜绿假单胞菌是一种机会性人类病原体，可在吞噬细胞缺陷或受损的人群中引起严重感染。我们已经开发出光学透明且基因可操作的斑马鱼胚胎作为铜绿假单胞菌系统性感染的模型。尽管在这个发育阶段缺乏适应性免疫，斑马鱼胚胎对铜绿假单胞菌感染具有高度抗性，但与人类一样，吞噬细胞的耗竭极大地增加了它们的易感性。缺乏功能性III型分泌系统的减毒铜绿假单胞菌菌株的毒力在吞噬细胞耗竭时得以恢复，这表明该系统通过其对吞噬细胞的作用影响毒力。活体成像显示细菌与多种血细胞类型相互作用。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在抗感染保护中都起作用。感染后立即观察到红细胞和其他血细胞在血管内聚集并导致循环阻塞，这可能与人类铜绿假单胞菌感染的血栓性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基因可操作性应能阐明在中性粒细胞减少或吞噬细胞功能受损的情况下铜绿假单胞菌发病机制的分子和细胞细节。
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.
登录
查看更多内容
影响因子：
3.8
作者：
Fauvarque, MO;Bergeret, E;Attree, I
通讯作者：
Attree, I
影响因子：
2.7
作者：
Bates, Jennifer M.;Mittge, Erika;Guillemin, Karen
通讯作者：
Guillemin, Karen
影响因子：
3.6
作者：
Lin, Bin;Chen, Shangwu;Xu, Anlong
通讯作者：
Xu, Anlong
影响因子：
3.6
作者：
FinckBarbancon, V;Goranson, J;Frank, DW
通讯作者：
Frank, DW
DOI：
10.1073/pnas.96.26.15202
发表时间：
1999-12-21
影响因子：
11.1
作者：
Darby, C;Cosma, CL;Manoil, C
通讯作者：
Manoil, C