Shelton W Wright, Sineenart Sengyee, Peeraya Ekchariyawat, Rungnapa Phunpang, Adul Dulsuk, Guilhem Rerolle, Abdullah Bashmail, Narisara Chantratita, Sina A Gharib, T Eoin West
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引用次数: 0
摘要
肺美拉德氏病是一种由假马来伯克霍尔德氏菌引起的严重热带感染,尽管早期接受抗生素治疗,但死亡率仍很高。γδT细胞越来越多地被认为是细菌性肺炎期间宿主中性粒细胞反应的驱动因素,但它们在肺圆线虫病中的作用尚不清楚。在这里,我们报告说,在类鼻疽患者中,即使调整了疾病的严重程度,较低的外周血γδ T 细胞浓度也与较高的死亡率相关。γδT细胞也在肺部富集,并在肺部类黑质病小鼠模型中保护患者免于死亡。受感染的小鼠体内缺乏γδ T 细胞会诱导中性粒细胞早期进入肺部,这与细菌负担无关。随后,γδ T 细胞缺乏导致肺部与中性粒细胞相关的炎症加剧,细菌清除能力受损。此外,γδ T 细胞还影响感染后肺部中性粒细胞的功能和亚群多样性。我们的研究结果表明,γδ T 细胞通过调节过度的中性粒细胞相关炎症,在重症细菌性肺炎期间对肺部起到了新的保护作用。
γδ T Cells Mediate Protection against Neutrophil-associated Lung Inflammation in Pulmonary Melioidosis.
Pulmonary melioidosis is a severe tropical infection caused by Burkholderia pseudomallei and is associated with high mortality, despite early antibiotic treatment. γδ T cells have been increasingly implicated as drivers of the host neutrophil response during bacterial pneumonia, but their role in pulmonary melioidosis is unknown. Here, we report that in patients with melioidosis, a lower peripheral blood γδ T-cell concentration is associated with higher mortality, even when adjusting for severity of illness. γδ T cells were also enriched in the lung and protected against mortality in a mouse model of pulmonary melioidosis. γδ T-cell deficiency in infected mice induced an early recruitment of neutrophils to the lung, independent of bacterial burden. Subsequently, γδ T-cell deficiency resulted in increased neutrophil-associated inflammation in the lung as well as impaired bacterial clearance. In addition, γδ T cells influenced neutrophil function and subset diversity in the lung after infection. Our results indicate that γδ T cells serve a novel protective role in the lung during severe bacterial pneumonia by regulating excessive neutrophil-associated inflammation.
期刊介绍:
The American Journal of Respiratory Cell and Molecular Biology publishes papers that report significant and original observations in the area of pulmonary biology. The focus of the Journal includes, but is not limited to, cellular, biochemical, molecular, developmental, genetic, and immunologic studies of lung cells and molecules.