Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo
Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo
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DOI：
10.4049/jimmunol.174.6.3643
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发表时间：
2005-03-15
影响因子：
4.4
通讯作者：
Whyte, MKB
中科院分区：
文献类型：
--
作者：
Allen, L;Dockrell, DH;Whyte, MKB
中性粒细胞从发炎部位的清除对于炎症的消退是至关重要的，但是病原体驱动的中性粒细胞凋亡可以损害宿主的防御。我们以前表明，绿脓菌素，吩嗪有毒代谢产物产生的铜绿假单胞菌，加速体外中性粒细胞凋亡。我们在急性肺炎的小鼠模型中比较了铜绿假单胞菌的野生型和绿脓菌素缺陷型菌株。肺内滴注任一株铜绿假单胞菌均可导致支气管肺泡灌洗液中性粒细胞计数迅速增加，直至感染后18 h。在野生型感染中，中性粒细胞数量随后稳步下降，而在感染绿脓杆菌缺陷型铜绿假单胞菌的小鼠中，中性粒细胞数量增加至48小时。与这些差异一致，绿脓菌素的产生与肺部细菌清除率降低有关。与吩嗪缺陷菌株或另外两种缺乏绿脓菌素生产但产生其他吩嗪的菌株相比，野生型感染小鼠的神经细胞凋亡增加。与吩嗪缺陷株感染小鼠相比，在18 h时，野生型中有效的中性粒细胞趋化因子（MIP-2，KC）和细胞因子（IL-6，IL-113）的浓度显著降低。我们的结论是绿脓杆菌生产抑制急性炎症反应的病原体驱动的加速中性粒细胞凋亡和减少局部炎症，这是有利的细菌的生存。免疫学杂志，2005，174：3643-3649.
Clearance of neutrophils from inflamed sites is critical for resolution of inflammation, but pathogen-driven neutrophil apoptosis can impair host defenses. We previously showed that pyocyanin, a phenazine toxic metabolite produced by Pseudomonas aeruginosa, accelerates neutrophil apoptosis in vitro. We compared wild-type and pyocyanin-deficient strains of P. aeruginosa in a murine model of acute pneumonia. Intratracheal instillation of either strain of P. aeruginosa caused a rapid increase in bronchoalveolar lavage neutrophil counts up to 18 h after infection. In wild-type infection, neutrophil numbers then declined steadily, whereas neutrophil numbers increased up to 48 h in mice infected with pyocyanin-deficient P. aeruginosa. In keeping with these differences, pyocyanin production was associated with reduced bacterial clearance from the lungs. Neutrophil apoptosis was increased in mice infected with wild-type compared with the phenazine-deficient strain or two further strains that lack pyocyanin production, but produce other phenazines. Concentrations of potent neutrophil chemokines (MIP-2, KC) and cytokines (IL-6, IL-113) were significantly lower in wild-type compared with phenazine-deficient strain-infected mice at 18 h. We conclude that pyocyanin production by P. aeruginosa suppresses the acute inflammatory response by pathogen-driven acceleration of neutrophil apoptosis and by reducing local inflammation, and that this is advantageous for bacterial survival. The Journal of Immunology, 2005, 174: 3643-3649.