Protective role of Mincle in bacterial pneumonia by regulation of neutrophil mediated phagocytosis and extracellular trap formation.
Protective role of Mincle in bacterial pneumonia by regulation of neutrophil mediated phagocytosis and extracellular trap formation.
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发表时间：
2014
影响因子：
6.4
通讯作者：
Atul Sharma;Anthony L. Steichen;C. Jondle;B. Mishra;Jyotika Sharma
中科院分区：
文献类型：
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作者：
Atul Sharma;Anthony L. Steichen;C. Jondle;B. Mishra;Jyotika Sharma
肺炎克雷伯菌医院感染是革兰阴性菌败血症的常见原因。为了了解宿主先天性免疫成分在这种疾病中的功能，我们研究了C型凝集素受体Mincle在K.肺炎。方法在野生型和Mincle（-/-）小鼠肺部感染K。pneumoniae进行比较。结果：感染亚致死剂量细菌的野生型小鼠可以通过细菌清除和调节宿主反应来解决感染，而Mincle（-/-）小鼠高度易感，细菌负荷逐渐增加，尽管它们能够引起炎症反应，随着严重肺炎的发作而转变为过度炎症。这与严重的肺部病理学相关，肺部中性粒细胞大量积聚。重要的是，Mincle（-/-）中性粒细胞显示出吞噬非调理细菌的能力缺陷和形成细胞外陷阱（NET）的能力受损，细胞外陷阱是中性粒细胞对抗入侵病原体（包括K.肺炎。结论Mincle在宿主防御K.肺炎通过协调中性粒细胞的细菌清除机制。Mincle在调节中性粒细胞NET形成中的新作用可能对以NET形成失调为特征的慢性疾病状况有影响。
BACKGROUND Nosocomial infections with Klebsiella pneumoniae are a frequent cause of Gram-negative bacterial sepsis. To understand the functioning of host innate immune components in this disorder, we examined a previously uninvestigated role of the C-type lectin receptor Mincle in pneumonic sepsis caused by K. pneumoniae. METHODS Disease progression in wild-type and Mincle(-/-) mice undergoing pulmonary infection with K. pneumoniae was compared. RESULTS Whereas the wild-type mice infected with a sublethal dose of bacteria could resolve the infection with bacterial clearance and regulated host response, the Mincle(-/-) mice were highly susceptible with a progressive increase in bacterial burden, despite their ability to mount an inflammatory response that turned to an exaggerated hyperinflammation with the onset of severe pneumonia. This correlated with severe lung pathology with a massive accumulation of neutrophils in their lungs. Importantly, Mincle(-/-) neutrophils displayed a defective ability to phagocytize nonopsonic bacteria and an impaired ability to form extracellular traps (NETs), an important neutrophil function against invading pathogens, including K. pneumoniae. CONCLUSION Our results demonstrate protective role of Mincle in host defense against K. pneumoniae pneumonia by coordinating bacterial clearance mechanisms of neutrophils. A novel role for Mincle in the regulation of neutrophil NET formation may have implications in chronic disease conditions characterized by deregulated NET formation.