Institut National de la Santé et de la Recherche Médicale (INSERM), U945, Université Pierre et Marie Curie-Paris 6, Paris, France.
J Infect Dis. 2012 Apr 1;205(7):1163-72. doi: 10.1093/infdis/jis031. Epub 2012 Feb 21.
For years, the analysis of innate responses to the major mold pathogen Aspergillus fumigatus has been restricted to specialized cells, such as professional phagocytes. More recently, the contribution of the airway epithelial barrier has been assessed and studies have shown that it was able to sense and react to the Aspergillus infection, for example, by producing cytokines.
To further explore the reaction of the respiratory epithelium to the fungus, we analyzed the proteome response of a human bronchial epithelial cell line to Aspergillus infection using difference gel electrophoresis. We studied the protein pattern of BEAS-2B cell culture supernatant after interaction of the cells with Aspergillus during a 15-hour coculture.
We found formerly unknown aspects of bronchial cell behavior during Aspergillus infection: bronchial cells are able to develop both cellular defense mechanisms (ie, thioredoxin system activation) and immune reactions (ie, lysosomal degranulation and cathepsin activation) in response to the fungal aggression.
Bronchial epithelial cells appear to be a more important effector of antifungal defense than expected. Degranulation of lysosomal enzymes that might be responsible for both fungal growth inhibition and host cell damage suggests that inductors/inhibitors of these pathways may be potential targets of therapeutic intervention.
多年来，对主要霉菌病原体烟曲霉固有反应的分析一直局限于专业吞噬细胞等特殊细胞。最近，气道上皮屏障的贡献已经得到了评估，研究表明它能够感知和对曲霉感染作出反应，例如，通过产生细胞因子。
为了进一步探索呼吸道上皮对真菌的反应，我们使用差异凝胶电泳分析了人支气管上皮细胞系对烟曲霉感染的蛋白质组反应。我们研究了 BEAS-2B 细胞与曲霉在 15 小时共培养过程中相互作用后细胞培养上清液的蛋白质图谱。
我们发现了支气管细胞在烟曲霉菌感染过程中以前未知的行为方面：支气管细胞能够针对真菌的侵袭，发展细胞防御机制（例如，硫氧还蛋白系统激活）和免疫反应（例如，溶酶体脱颗粒和组织蛋白酶激活）。
支气管上皮细胞似乎是抗真菌防御的比预期更重要的效应器。溶酶体酶的脱颗粒可能负责真菌生长抑制和宿主细胞损伤，这表明这些途径的诱导剂/抑制剂可能是治疗干预的潜在靶点。
