Absence of the lectin activation pathway of complement does not increase susceptibility to Pseudomonas aeruginosa infections
Absence of the lectin activation pathway of complement does not increase susceptibility to Pseudomonas aeruginosa infections
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DOI：
10.1016/j.imbio.2011.10.001
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发表时间：
2012-02-01
期刊：
影响因子：
2.8
通讯作者：
Schwaeble, Wilhelm J.
中科院分区：
文献类型：
--
作者：
Kenawy, Hany Ibrahim;Ali, Youssif Mohammed;Schwaeble, Wilhelm J.
铜绿假单胞菌仍然是加重免疫功能低下和囊性纤维化患者负担的主要临床病原体之一。本研究旨在确定补体凝集素途径在侵袭性肺炎小鼠模型中对铜绿假单胞菌免疫防御中的作用。利用三种补体途径的体外实验，我们证明了一些铜绿假单胞菌株结合凝集素途径识别亚组分，并以凝集素途径特异性的方式启动补体激活。所有受试菌株都通过经典途径和替代途径激活补体。我们通过在小鼠鼻内感染模型中测试凝集素途径激活菌株来评估凝集素途径激活在对抗铜绿假单胞菌感染中的重要性。没有凝集素途径活性的MASP2(甘露聚糖结合凝集素相关丝氨酸蛋白酶-2)缺陷小鼠与野生型小鼠相比没有明显的生存劣势(分别为72.7%和81.8%，p=0.48)。同样，在MASP-2充足和MASP-2缺乏的小鼠血清之间没有发现调理活性的差异。此外，在整个铜绿假单胞菌感染过程中，WT小鼠和MASP-2-/-小鼠的肺部细胞因子表达谱相似。我们得出结论，凝集素途径在对抗小鼠铜绿假单胞菌感染中不起重要作用。(C)2011年爱思唯尔股份有限公司。版权所有。
Pseudomonas aeruginosa remains one of the major clinical pathogens that burden immuno-compromised patients and patients with cystic fibrosis. The present study aimed to define the role of the lectin pathway of complement in the immune-defence against P. aeruginosa in a mouse model of invasive pneumonia. Using in vitro assays specific for each of the three complement pathways, we demonstrate that some strains of P. aeruginosa bind lectin pathway recognition sub-components and initiate complement activation in a lectin pathway-specific mode. All of the tested strains activated complement via classical and alternative pathways. We assessed the importance of lectin pathway activation in fighting P. aeruginosa infections by testing a lectin pathway activating strain in a mouse model of intra-nasal infection. MASP2 (mannan binding lectin associated serine protease-2) deficient mice, which have no lectin pathway activity, had no significant survival disadvantage compared to wild type littermates (72.7% and 81.8% survival, respectively, p = 0.48). Likewise, no difference in opsonising activity was seen between MASP-2 sufficient and MASP-2 deficient mouse sera. Moreover, cytokine expression profiles in the lungs of WT mice and MASP-2-/- mice were similar throughout the course of P. aeruginosa infection. We conclude that the lectin pathway does not play an essential role in fighting P. aeruginosa infection in mice. (C) 2011 Elsevier GmbH. All rights reserved.