GM-CSF in the Lung Protects against Lethal Influenza Infection
GM-CSF in the Lung Protects against Lethal Influenza Infection
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DOI：
10.1164/rccm.201012-2036oc
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发表时间：
2011-07-15
影响因子：
24.7
通讯作者：
Shams, Homayoun
中科院分区：
文献类型：
--
作者：
Huang, Fang-Fang;Barnes, Peter F.;Shams, Homayoun
原理：在动物模型中，肺泡巨噬细胞有助于宿主防御流感。增强肺泡巨噬细胞功能可能有助于保护免受influenza.Objectives：To determine if increased expression of granulocyte/macrophagecolony-stimulating factor（GM-CSF）in the lung increases to resistance to influenza.Methods：野生型小鼠和转基因小鼠表达GM-CSF在肺感染流感病毒，肺病理，体重减轻，死亡率进行了测量。我们还管理GM-CSF的野生型小鼠感染流感病毒的肺部。测量和主要结果：野生型小鼠感染不同株的流感病毒后全部死亡，但所有转基因小鼠表达GM-CSF的肺部存活。后者也大大减少了体重减轻和肺损伤，并显示出控制感染的快速宿主炎症反应的组织学证据。转基因小鼠对流感的抵抗力通过消除肺泡吞噬细胞而被消除，但不是通过T细胞、B细胞或中性粒细胞的耗竭。转基因小鼠的肺泡巨噬细胞比野生型小鼠多得多，它们对流感诱导的细胞凋亡更具抵抗力。递送鼻内GM-CSF到野生型小鼠也赋予抵抗influenza.Conclusions：GM-CSF赋予抵抗流感通过增强依赖于肺泡巨噬细胞的先天免疫机制。这种细胞因子的肺部递送具有降低流感病毒引起的发病率和死亡率的潜力。
Rationale: Alveolar macrophages contribute to host defenses against influenza in animal models. Enhancing alveolar macrophage function may contribute to protection against influenza.Objectives: To determine if increased expression of granulocyte/macrophagecolony-stimulating factor (GM-CSF) in the lung increases resistance to influenza.Methods: Wild-type mice and transgenic mice that expressed GM-CSF in the lung were infected with influenza virus, and lung pathology, weight loss, and mortality were measured. We also administered GM-CSF to the lungs of wild-type mice that were infected with influenza virus.Measurements and Main Results: Wild-type mice all died after infection with different strains of influenza virus, but all transgenic mice expressing GM-CSF in the lungs survived. The latter also had greatly reduced weight loss and lung injury, and showed histologic evidence of a rapid host inflammatory response that controlled infection. The resistance of transgenic mice to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T cells, B cells, or neutrophils. Transgenic mice had far more alveolar macrophages than did wild-type mice, and they were more resistant to influenza induced apoptosis. Delivery of intranasal GM-CSF to wild-type mice also conferred resistance to influenza.Conclusions: GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.