Spatial characteristics of CD169+ resident conducting airway macrophages during Aspergillus fumigatus-induced inflammation

CD169+ resident tissue macrophages reportedly prevent excessive neutrophil-mediated response by cloaking the damaged tissues in the site of inflammation. Such macrophages were demonstrated to maintain the homeostasis in the peritoneum (Uderhardt S. et al. Cell. 2019; 18;177(3):541-555), however, their role in airway inflammation is not characterized. In this study, we investigate the implication of CD169+ resident conducting airway macrophages in the inflammatory response induced by inhalation of Aspergillus fumigatus conidia. Since the airway epithelium is exposed to inhaled pathogens, we aimed to examine whether these macrophages contribute to the epithelium defense. C57BL/6 mice received an oropharyngeal application of A. fumigatus conidia. The lungs were fixed and conducting airways were stained immunohistochemically. Three-dimensional images were obtained using fluorescent confocal laser scanning microscopy. In intact mice, we identified CD169+CD11c– resident conducting airway macrophages possessing special irregular morphology beneath the smooth muscles and in close proximity to them, however, not in contact with epithelium. Moreover, resident macrophages were separated from the epithelium with basement membrane and smooth muscle layer in the acute and the late stage of A. fumigatus conidia-induced inflammation. While CD11c+ intraepithelial dendritic cells interacted with invading airway mucosa neutrophils, resident macrophages did not change their location beneath the smooth muscles. Thus, in A. fumigatus conidia-induced airway inflammation, resident conducting airway macrophages are unlikely to prevent the damage of the airway epithelium or the basement membrane but might control the integrity of the smooth muscle layer. The work was funded by RFBR, project 20-04-60311.