Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages
Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages
复制标题
DOI：
10.1128/iai.71.2.891-903.2003
复制
发表时间：
2003-02-01
影响因子：
3.1
通讯作者：
Latgé, JP
中科院分区：
文献类型：
--
作者：
Ibrahim-Granet, O;Philippe, B;Latgé, JP
烟曲霉是最普遍的空气传播真菌病原体负责致命的侵袭性曲霉病在免疫受损的病人。烟曲霉的分生孢子到达肺泡后，被肺泡巨噬细胞（肺的主要吞噬细胞）吞噬。采用电镜和免疫荧光分析了烟曲霉分生孢子在小鼠肺泡巨噬细胞MH-S和人肺泡巨噬细胞中的吞噬和细胞内运输。烟曲霉分生孢子的吞噬作用需要肌动蛋白聚合和磷脂酰肌醇3-激酶活性。用转铁蛋白受体、早期核内体抗原和Rab7特异性标记物进行免疫标记，证实烟曲霉吞噬体与早期和晚期核内体融合。采用固定式嗜酸探针LysoTracker Red DND-99和抗组织蛋白酶D抗体监测烟曲霉吞噬溶酶体的成熟情况。巴菲霉素a诱导的溶酶体酸化抑制可消除巨噬细胞对分生孢子的杀伤。这些数据表明烟曲霉吞噬体的成熟是与内吞途径的室室融合的结果，分生孢子的杀死取决于吞噬溶酶体的酸化。在此基础上提出了一种烟曲霉分生孢子被肺泡巨噬细胞吞噬的模型。
Aspergillus fumigatus is the most prevalent airborne fungal pathogen responsible for fatal invasive aspergillosis in inummocompromised patients. Upon arrival in the lung alveolus, conidia of A. fumigatus are phagocytosed by alveolar macrophages, the major phagocytic cells of the lung. Engulfment and intracellular trafficking of A. fumigatus conidia in alveolar macrophages of two different origins, the murine cell line MH-S and human pulmonary alveolar macrophages, were analyzed by electron microscopy and immunofluorescence. Phagocytosis of A. fumigatus conidia required actin polymerization and phosphatidylinositol 3-kinase activity. Fusion of A. fumigatus phagosomes with early and late endosomes was shown by immunolabeling with specific markers for the transferrin receptor, early endosome antigen, and Rab7. Maturation of A. fumigatus phagolysosomes was monitored by using a fixable acidotropic probe, LysoTracker Red DND-99, and an anti-cathepsin D antibody. Bafilomycin A-induced inhibition of lysosomal acidification abolished the conidial killing by the macrophages. These data suggest that the maturation of A. fumigatus phagosomes results from fusion with the compartments of the endocytic pathway and that the killing of conidia depends on phagolysosome acidification. A model for the phagocytosis of A. fumigatus conidia by alveolar macrophages is proposed on the basis of these results.