Depletion of Natural Killer Cells Increases Mice Susceptibility in a Pseudomonas aeruginosa Pneumonia Model
Depletion of Natural Killer Cells Increases Mice Susceptibility in a Pseudomonas aeruginosa Pneumonia Model
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DOI：
10.1097/ccm.0000000000000311
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发表时间：
2014-06-01
影响因子：
8.8
通讯作者：
Asehnoune, Karim
中科院分区：
文献类型：
--
作者：
Broquet, Alexis;Roquilly, Antoine;Asehnoune, Karim
目的：铜绿假单胞菌感染是一种临床相关的感染，涉及重症监护病房的肺炎。了解肺炎期间宿主启动的免疫反应类型将有助于确定干扰细菌致病性的新策略。在这种情况下，自然杀伤细胞的作用仍然存在争议。我们评估了系统性自然杀伤细胞在绿脓杆菌小鼠肺炎模型中的作用。设计：实验研究。设置：大学医院的研究实验室。受试者：RjOrl：SWISS和BALB/cJ小鼠（体重，20-24克）。通过细菌负荷、髓过氧化物酶活性、内皮通透性（肺水肿）、免疫细胞浸润（组织学分析）、促炎细胞因子释放和Ly 6-G免疫组织化学评估肺损伤。在肺和脾中评估细菌负荷。自然杀伤细胞的数量和状态进行了评估脾脏（流式细胞术和定量聚合酶链反应）。耗尽的自然杀伤细胞是通过IV抗去唾液酸-GM 1抗体injection.Measurements和主要结果：铜绿假单胞菌气管滴注导致急性肺炎与肺中的细菌负荷的快速下降，并与内皮细胞通透性的增加，促炎细胞因子（肿瘤坏死因子-和白细胞介素-1），髓过氧化物酶的活性，然后由Ly 6-G阳性细胞浸润在肺。在脾脏中检测到铜绿假单胞菌。在铜绿假单胞菌感染过程中，脾脏自然杀伤细胞的活化和成熟的膜标志物（CD 69和KLRG 1分子）增加。脾自然杀伤细胞在铜绿假单胞菌感染后激活产生干扰素，但不产生白细胞介素10。最终，自然杀伤细胞耗竭的小鼠显示出肺部中性粒细胞数量增加，死亡率增加，而肺部细菌负荷没有改变，这表明自然杀伤细胞耗竭的小鼠与对照动物相比更容易感染。我们首次报道了自然杀伤细胞在小鼠对铜绿假单胞菌诱导的急性肺炎模型的易感性中起主要作用。
Objectives:Pseudomonas aeruginosa infection is a clinically relevant infection involved in pneumonia in ICUs. Understanding the type of immune response initiated by the host during pneumonia would help defining new strategies to interfere with the bacteria pathogenicity. In this setting, the role of natural killer cells remains controversial. We assessed the role of systemic natural killer cells in a Pseudomonas aeruginosa mouse pneumonia model.Design: Experimental study.Setting: Research laboratory from a university hospital.Subjects: RjOrl:SWISS and BALB/cJ mice (weight, 20-24 g).Interventions: Lung injuries were assessed by bacterial load, myeloperoxidase activity, endothelial permeability (pulmonary edema), immune cell infiltrate (histological analysis), proinflammatory cytokine release, and Ly6-G immunohistochemistry. Bacterial loads were assessed in the lungs and spleen. Natural killer cell number and status were assessed in spleen (flow cytometry and quantitative polymerase chain reaction). Depletion of natural killer cells was achieved through an IV anti-asialo-GM1 antibody injection.Measurements and Main Results:Pseudomonas aeruginosa tracheal instillation led to an acute pneumonia with a rapid decrease of bacterial load in lungs and with an increase of endothelial permeability, proinflammatory cytokines (tumor necrosis factor- and interleukin-1), and myeloperoxidase activity followed by Ly6-G positive cell infiltrate in lungs. Pseudomonas aeruginosa was detected in the spleen. Membrane markers of activation and maturation (CD69 and KLRG1 molecules) were increased in splenic natural killer cells during Pseudomonas aeruginosa infection. Splenic natural killer cells activated upon Pseudomonas aeruginosa infection produced interferon- but not interleukin-10. Ultimately, mice depleted of natural killer cells displayed an increased neutrophil numbers in the lungs and an increased mortality rate without bacterial load modifications in the lungs, indicating that mice depleted of natural killer cells were much more susceptible to infection compared with control animals.Conclusions: We report for the first time that natural killer cells play a major role in the mice susceptibility toward a Pseudomonas aeruginosa-induced acute pneumonia model.