Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells
ABSTRACT During the initiation of invasive aspergillosis, inhaled Aspergillus fumigatus conidia are deposited on the epithelial cells lining the bronchi, terminal bronchioles, and alveoli. While the interactions of A. fumigatus with bronchial and type II alveolar cell lines have been investigated in...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-10-01
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| Series: | mSphere |
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| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00314-23 |
| _version_ | 1797651071900844032 |
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| author | Hong Liu Jianfeng Lin Quynh T. Phan Fabrice N. Gravelat Donald C. Sheppard Scott G. Filler |
| author_facet | Hong Liu Jianfeng Lin Quynh T. Phan Fabrice N. Gravelat Donald C. Sheppard Scott G. Filler |
| author_sort | Hong Liu |
| collection | DOAJ |
| description | ABSTRACT During the initiation of invasive aspergillosis, inhaled Aspergillus fumigatus conidia are deposited on the epithelial cells lining the bronchi, terminal bronchioles, and alveoli. While the interactions of A. fumigatus with bronchial and type II alveolar cell lines have been investigated in vitro, 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 in vitro model to study the interaction of two strains of A. fumigatus with these cells. We then compared the interactions of A. fumigatus with the A549 type II alveolar epithelial cell line and the HSAE cell line. We found that A. fumigatus conidia were poorly endocytosed by A549 cells, but avidly endocytosed by HSAE cells. A. fumigatus germlings invaded both cell types by induced endocytosis, but not by active penetration. A549 cell endocytosis of A. fumigatus was independent of fungal viability, more dependent on host microfilaments than microtubules, and induced by A. fumigatus 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 A. fumigatus germlings and by secreted fungal products. In response to A. fumigatus 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 A. fumigatus with bronchiolar epithelial cells in vitro. Importance During the initiation of invasive aspergillosis, Aspergillus fumigatus interacts with the epithelial cells that line the airways and alveoli. Previous studies of A. fumigatus-epithelial cell interactions in vitro 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 in vitro model of the interactions of A. fumigatus with bronchiolar epithelial cells. We discovered that A. fumigatus invades and damages A549 and HSAE cell lines by distinct mechanisms. Also, the proinflammatory responses of the cell lines to A. fumigatus are different. These results provide insight into how A. fumigatus interacts with different types of epithelial cells during invasive aspergillosis and demonstrate that HSAE cells are useful in vitro model for investigating the interactions of this fungus with bronchiolar epithelial cells. |
| first_indexed | 2024-03-11T16:09:45Z |
| format | Article |
| id | doaj.art-ec3c38c7baaa4fb9b276cb2d53534c77 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-03-11T16:09:45Z |
| publishDate | 2023-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-ec3c38c7baaa4fb9b276cb2d53534c772023-10-24T16:32:15ZengAmerican Society for MicrobiologymSphere2379-50422023-10-018510.1128/msphere.00314-23Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cellsHong Liu0Jianfeng Lin1Quynh T. Phan2Fabrice N. Gravelat3Donald C. Sheppard4Scott G. Filler5The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center , Torrance, California, USAThe Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center , Torrance, California, USAThe Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center , Torrance, California, USADepartment of Medicine, Infectious Diseases, and Immunity in Global Health Program, Research Institute of the McGill University Health Centre , Montreal, Quebec, CanadaDepartment of Medicine, Infectious Diseases, and Immunity in Global Health Program, Research Institute of the McGill University Health Centre , Montreal, Quebec, CanadaThe Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center , Torrance, California, USAABSTRACT During the initiation of invasive aspergillosis, inhaled Aspergillus fumigatus conidia are deposited on the epithelial cells lining the bronchi, terminal bronchioles, and alveoli. While the interactions of A. fumigatus with bronchial and type II alveolar cell lines have been investigated in vitro, 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 in vitro model to study the interaction of two strains of A. fumigatus with these cells. We then compared the interactions of A. fumigatus with the A549 type II alveolar epithelial cell line and the HSAE cell line. We found that A. fumigatus conidia were poorly endocytosed by A549 cells, but avidly endocytosed by HSAE cells. A. fumigatus germlings invaded both cell types by induced endocytosis, but not by active penetration. A549 cell endocytosis of A. fumigatus was independent of fungal viability, more dependent on host microfilaments than microtubules, and induced by A. fumigatus 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 A. fumigatus germlings and by secreted fungal products. In response to A. fumigatus 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 A. fumigatus with bronchiolar epithelial cells in vitro. Importance During the initiation of invasive aspergillosis, Aspergillus fumigatus interacts with the epithelial cells that line the airways and alveoli. Previous studies of A. fumigatus-epithelial cell interactions in vitro 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 in vitro model of the interactions of A. fumigatus with bronchiolar epithelial cells. We discovered that A. fumigatus invades and damages A549 and HSAE cell lines by distinct mechanisms. Also, the proinflammatory responses of the cell lines to A. fumigatus are different. These results provide insight into how A. fumigatus interacts with different types of epithelial cells during invasive aspergillosis and demonstrate that HSAE cells are useful in vitro model for investigating the interactions of this fungus with bronchiolar epithelial cells.https://journals.asm.org/doi/10.1128/msphere.00314-23Aspergillus fumigatusalveolar epithelial cellsmall airway epithelial cellendocytosishost cell damagecytokine |
| spellingShingle | Hong Liu Jianfeng Lin Quynh T. Phan Fabrice N. Gravelat Donald C. Sheppard Scott G. Filler Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells mSphere Aspergillus fumigatus alveolar epithelial cell small airway epithelial cell endocytosis host cell damage cytokine |
| title | Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells |
| title_full | Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells |
| title_fullStr | Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells |
| title_full_unstemmed | Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells |
| title_short | Use of a human small airway epithelial cell line to study the interactions of Aspergillus fumigatus with pulmonary epithelial cells |
| title_sort | use of a human small airway epithelial cell line to study the interactions of aspergillus fumigatus with pulmonary epithelial cells |
| topic | Aspergillus fumigatus alveolar epithelial cell small airway epithelial cell endocytosis host cell damage cytokine |
| url | https://journals.asm.org/doi/10.1128/msphere.00314-23 |
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