Use of a Human Small Airway Epithelial Cell Line to Study the Interactions of with Pulmonary Epithelial Cells

During the initiation of invasive aspergillosis, inhaled conidia are deposited on the epithelial cells lining the bronchi, terminal bronchioles, and alveoli. While the interactions of with bronchial and type II alveolar cell lines have been investigated , little is known about the interactions of this fungus with terminal bronchiolar epithelial cells. Using the HSAEC1-KT human small airway epithelial (HSAE) cell line, we developed an model to study the interaction of two strains of with these cells. We then compared the interactions of with the A549 type II alveolar epithelial cell line and the HSAE cell line. We found that conidia were poorly endocytosed by A549 cells, but avidly endocytosed by HSAE cells. germlings invaded both cell types by induced endocytosis, but not by active penetration. A549 cell endocytosis of was independent of fungal viability, more dependent on host microfilaments than microtubules, and induced by CalA interacting with host cell integrin α5β1. By contrast, HSAE cell endocytosis required fungal viability, was more dependent on microtubules than microfilaments, and did not require CalA or integrin α5β1. HSAE cells were more susceptible than A549 cells to damage caused by direct contact with killed germlings and by secreted fungal products. In response to infection, A549 cells secreted a broader profile of cytokines and chemokines than HSAE cells. Taken together, these results demonstrate that studies of HSAE cells provide complementary data to A549 cells and thus represent a useful model for probing the interactions of with bronchiolar epithelial cells . Importance During the initiation of invasive aspergillosis, interacts with the epithelial cells that line the airways and alveoli. Previous studies of -epithelial cell interactions used either large airway epithelial cell lines or the A549 type II alveolar epithelial cell line; the interactions of fungi with terminal bronchiolar epithelial cells were not investigated. Using the TERT-immortalized human small airway epithelial HSAEC1-KT (HSAE) cell line, we developed an model of the interactions of with bronchiolar epithelial cells. We discovered that invades and damages A549 and HSAE cell lines by distinct mechanisms. Also, the proinflammatory responses of the cell lines to are different. These results provide insight into how interacts with different types of epithelial cells during invasive aspergillosis and demonstrate that HSAE cells are useful model for investigating the interactions of this fungus with bronchiolar epithelial cells.