Aspergillus species, most commonly A.fumigatus, are exogenous fungi and can colonize airway mucosa, particularly in patients with localized underlying bronchopulmonary disorders such as healed tuberculous cavities, cystic fibrosis and bronchiectasis, and occasionally invade the airway mucosa regardless of systemic immunocompromised conditions. However, the mechanisms of colonization and invasion of Aspergillus in the respiratory mucosa, especially the initial stage of interaction of Aspergillus with respiratory mucosa after inhalation of conidia through airways are still poorly understood. Interaction of a clinical isolate of A.fumigatus with human bronchial mucosa in an organ culture model with an air-mucosal interface was studied. A.fumigatus conidia were inoculated onto the organ culture tissues, and incubated for up to 24h in a humidified atmosphere containing 5% CO2 at 37. At each timepoint, after measuring the ciliary beat frequency (CBF) of bronchial mucosal epithelium by a photometric technique, adherence and invasion of the bronchial epithelium by A.fumigatus conidia (and hyphae) as well as structural changes of the epithelium were investigated by scanning and transmission electron microscopy. These studies demonstrated that A.fumigatus caused damage to bronchial epithelium including separation of intercellular junction, extrusion and detachment of ciliated cells from neighboring cells associated with CBF slowing, and also demonstrated that part of A.fumigatus conidia were internalized within ciliated and non-ciliated epithelial cells, and hyphae penetrated through both intercellular and intracellular spaces of the epithelium. These findings suggest that there might be at least three different pathways by which Aspergillus invades the bronchial mucosa internalization of conidia within epithelial cells (although the fate of the internalized conidia is still unclear), penetration of germinated conidia (or hyphae) through the intercellular space of ciliated epithelium, and direct penetration of hyphae through the intracellular space of the epithelial cells in association with destruction of the cytoplasmic membrane of the epithelial cells. Although we demonstrated serial morphological changes of both human bronchial epithelium and A.fumigatus conidia (and hyphae) using an organ culture model of human bronchial tissue with an air-mucosal interface, the precise mechanisms of colonization and invasion of A.fumigatus in human respiratory tracts still remain to be elucidated and further studies will be required.
Full conference title:
3rd Advances Against Aspergillosis
- AAA 3rd (2008)