Eosinophil Deficiency Compromises Lung Defense against Aspergillus fumigatus
Eosinophil Deficiency Compromises Lung Defense against Aspergillus fumigatus
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DOI：
10.1128/iai.01172-13
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发表时间：
2014-03-01
影响因子：
3.1
通讯作者：
Steele, Chad
中科院分区：
文献类型：
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作者：
Lilly, Lauren M.;Scopel, Michaella;Steele, Chad
暴露于霉菌烟曲霉可能导致过敏性支气管肺曲霉病，慢性坏死性肺曲霉病或侵袭性曲霉病（IA），这取决于宿主的免疫状态。神经元缺乏是发展IA的主要危险因素，IA是与A相关的最危及生命的疾病。烟毒暴露在这里，我们证明，除了中性粒细胞，嗜酸性粒细胞是一个重要的贡献者清除A。从肺里取出烟曲霉菌急性A.在正常小鼠中，烟曲霉菌激发诱导了CD 11b（+）Siglec F+ Ly-6 G（lo）Ly-6C（neg）CCR 3（+）嗜酸性粒细胞向肺的募集，这伴随着肺Epx（嗜酸性粒细胞过氧化物酶）mRNA水平的增加。转录因子dblGATA 1缺陷的小鼠表现出嗜酸性粒细胞的选择性缺陷，表现出A.烟曲霉清除和肺部萌发生物体的证据。高负荷与Epx（嗜酸性粒细胞过氧化物酶）和Prg 2（主要碱性蛋白）的mRNA表达降低以及白细胞介素1 β（IL-1 β）、IL-6、IL-17 A、粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和CXCL 1水平降低相关。然而，肺部炎症细胞群的检查未能证明dblGATA 1缺陷小鼠中单核细胞/巨噬细胞、树突状细胞或中性粒细胞募集的缺陷，这表明dlbGATA 1缺陷小鼠中嗜酸性粒细胞的缺乏是肺清除受损的唯一原因。我们发现，从骨髓产生的嗜酸性粒细胞对A。烟曲霉在体外，这不需要细胞接触，可以重演嗜酸性粒细胞全细胞裂解物。总的来说，我们的数据支持嗜酸性粒细胞在A.烟毒暴露
Exposure to the mold Aspergillus fumigatus may result in allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, or invasive aspergillosis (IA), depending on the host's immune status. Neutrophil deficiency is the predominant risk factor for the development of IA, the most life-threatening condition associated with A. fumigatus exposure. Here we demonstrate that in addition to neutrophils, eosinophils are an important contributor to the clearance of A. fumigatus from the lung. Acute A. fumigatus challenge in normal mice induced the recruitment of CD11b(+) Siglec F+ Ly-6G(lo) Ly-6C(neg) CCR3(+) eosinophils to the lungs, which was accompanied by an increase in lung Epx ( eosinophil peroxidase) mRNA levels. Mice deficient in the transcription factor dblGATA1, which exhibit a selective deficiency in eosinophils, demonstrated impaired A. fumigatus clearance and evidence of germinating organisms in the lung. Higher burden correlated with lower mRNA expression of Epx (eosinophil peroxidase) and Prg2 ( major basic protein) as well as lower interleukin 1 beta (IL-1 beta), IL-6, IL-17A, granulocyte colonystimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and CXCL1 levels. However, examination of lung inflammatory cell populations failed to demonstrate defects in monocyte/macrophage, dendritic cell, or neutrophil recruitment in dblGATA1-deficient mice, suggesting that the absence of eosinophils in dlbGATA1-deficient mice was the sole cause of impaired lung clearance. We show that eosinophils generated from bone marrow have potent killing activity against A. fumigtaus in vitro, which does not require cell contact and can be recapitulated by eosinophil whole-cell lysates. Collectively, our data support a role for eosinophils in the lung response after A. fumigatus exposure.