Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype.
Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype.
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DOI：
10.1371/journal.pone.0015943
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发表时间：
2011-01-05
期刊：
影响因子：
3.7
通讯作者：
Ray P
中科院分区：
文献类型：
--
作者：
Bhatia S;Fei M;Yarlagadda M;Qi Z;Akira S;Saijo S;Iwakura Y;van Rooijen N;Gibson GA;St Croix CM;Ray A;Ray P
普遍存在的真菌烟曲霉与慢性疾病有关，如免疫抑制患者的侵袭性肺曲霉病和囊性纤维化或严重哮喘患者的过敏性支气管肺曲霉病（ABPA）。由于持续暴露于这种真菌，宿主必须立即和决定性地进行免疫反应，以清除真菌孢子来抵御疾病。本研究中，我们观察到A.在烟曲霉中，肺泡巨噬细胞主要表达精氨酸酶1（Arg 1），这是交替激活的巨噬细胞（AAM）的关键标志物。还发现巨噬细胞表达也由AAM表达的Ym 1和CD 206，但不表达由经典活化的巨噬细胞表达的NOS 2。在AAM发生的已知信号传导轴IL-4 R α/STAT 6缺失的情况下，Arg 1的表达减少。虽然Dectin-1和TLR在细胞表面上的表达已被证明可以感知A.在烟曲霉中，真菌诱导的CD 11 c+肺泡巨噬细胞中的Arg 1表达不依赖于Dectin-1或通过大多数TLR介导细胞内信号传导的衔接子MyD 88。WT小鼠的肺泡巨噬细胞有效地吞噬真菌分生孢子，但Dectin-1缺陷小鼠的肺泡巨噬细胞显示真菌摄取受损。用氯膦酸盐填充的脂质体消耗巨噬细胞增加了感染小鼠的真菌负荷。总的来说，我们的研究表明，肺泡巨噬细胞，主要获得AAM表型后，A。烟曲霉感染，有保护作用，抵御这种真菌。
The ubiquitous fungus Aspergillus fumigatus is associated with chronic diseases such as invasive pulmonary aspergillosis in immunosuppressed patients and allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis or severe asthma. Because of constant exposure to this fungus, it is critical for the host to exercise an immediate and decisive immune response to clear fungal spores to ward off disease. In this study, we observed that rapidly after infection by A. fumigatus, alveolar macrophages predominantly express Arginase 1 (Arg1), a key marker of alternatively activated macrophages (AAMs). The macrophages were also found to express Ym1 and CD206 that are also expressed by AAMs but not NOS2, which is expressed by classically activated macrophages. The expression of Arg1 was reduced in the absence of the known signaling axis, IL-4Rα/STAT6, for AAM development. While both Dectin-1 and TLR expressed on the cell surface have been shown to sense A. fumigatus, fungus-induced Arg1 expression in CD11c+ alveolar macrophages was not dependent on either Dectin-1 or the adaptor MyD88 that mediates intracellular signaling by most TLRs. Alveolar macrophages from WT mice efficiently phagocytosed fungal conidia, but those from mice deficient in Dectin-1 showed impaired fungal uptake. Depletion of macrophages with clodronate-filled liposomes increased fungal burden in infected mice. Collectively, our studies suggest that alveolar macrophages, which predominantly acquire an AAM phenotype following A. fumigatus infection, have a protective role in defense against this fungus.
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影响因子：
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