Down syndrome is associated with altered frequency and functioning of tracheal multiciliated cells, and response to influenza virus infection
Summary: Individuals with Down syndrome (DS) clinically manifest severe respiratory illnesses; however, there is a paucity of data on how DS influences homeostatic physiology of lung airway, and its reactive responses to pulmonary pathogens. We generated well-differentiated ciliated airway epithelia...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223014384 |
| _version_ | 1827891570303565824 |
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| author | Samantha N. Thomas Brian F. Niemeyer Rocio J. Jimenez-Valdes Alexander J. Kaiser Joaquin M. Espinosa Kelly D. Sullivan Andrew Goodspeed James C. Costello Jonathan K. Alder Rodrigo Cañas-Arranz Adolfo García-Sastre Kambez H. Benam |
| author_facet | Samantha N. Thomas Brian F. Niemeyer Rocio J. Jimenez-Valdes Alexander J. Kaiser Joaquin M. Espinosa Kelly D. Sullivan Andrew Goodspeed James C. Costello Jonathan K. Alder Rodrigo Cañas-Arranz Adolfo García-Sastre Kambez H. Benam |
| author_sort | Samantha N. Thomas |
| collection | DOAJ |
| description | Summary: Individuals with Down syndrome (DS) clinically manifest severe respiratory illnesses; however, there is a paucity of data on how DS influences homeostatic physiology of lung airway, and its reactive responses to pulmonary pathogens. We generated well-differentiated ciliated airway epithelia using tracheas from wild-type and Dp(16)1/Yey mice in vitro, and discovered that Dp(16)1/Yey epithelia have significantly lower abundance of ciliated cells, an altered ciliary beating profile, and reduced mucociliary transport. Interestingly, both sets of differentiated epithelia released similar quantities of viral particles after infection with influenza A virus (IAV). However, RNA-sequencing and proteomic analyses revealed an immune hyperreactive phenotype particularly for monocyte-recruiting chemokines in Dp(16)1/Yey epithelia. Importantly, when we challenged mice in vivo with IAV, we observed immune hyper-responsiveness in Dp(16)1/Yey mice, evidenced by higher quantities of lung airway infiltrated monocytes, and elevated levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid. Our findings illuminate mechanisms underlying DS-mediated pathophysiological changes in airway epithelium. |
| first_indexed | 2024-03-12T21:27:41Z |
| format | Article |
| id | doaj.art-706040d3364d4b668e1e4718fba86159 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T21:27:41Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-706040d3364d4b668e1e4718fba861592023-07-28T04:26:32ZengElsevieriScience2589-00422023-08-01268107361Down syndrome is associated with altered frequency and functioning of tracheal multiciliated cells, and response to influenza virus infectionSamantha N. Thomas0Brian F. Niemeyer1Rocio J. Jimenez-Valdes2Alexander J. Kaiser3Joaquin M. Espinosa4Kelly D. Sullivan5Andrew Goodspeed6James C. Costello7Jonathan K. Alder8Rodrigo Cañas-Arranz9Adolfo García-Sastre10Kambez H. Benam11Department of Bioengineering, University of Colorado Denver, Aurora, CO 80045, USADivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USADivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Bioengineering, University of Colorado Denver, Aurora, CO 80045, USALinda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USALinda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; University of Colorado Comprehensive Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USALinda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; University of Colorado Comprehensive Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USADivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA; Linda Crnic Institute for Down Syndrome, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA; Corresponding authorSummary: Individuals with Down syndrome (DS) clinically manifest severe respiratory illnesses; however, there is a paucity of data on how DS influences homeostatic physiology of lung airway, and its reactive responses to pulmonary pathogens. We generated well-differentiated ciliated airway epithelia using tracheas from wild-type and Dp(16)1/Yey mice in vitro, and discovered that Dp(16)1/Yey epithelia have significantly lower abundance of ciliated cells, an altered ciliary beating profile, and reduced mucociliary transport. Interestingly, both sets of differentiated epithelia released similar quantities of viral particles after infection with influenza A virus (IAV). However, RNA-sequencing and proteomic analyses revealed an immune hyperreactive phenotype particularly for monocyte-recruiting chemokines in Dp(16)1/Yey epithelia. Importantly, when we challenged mice in vivo with IAV, we observed immune hyper-responsiveness in Dp(16)1/Yey mice, evidenced by higher quantities of lung airway infiltrated monocytes, and elevated levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid. Our findings illuminate mechanisms underlying DS-mediated pathophysiological changes in airway epithelium.http://www.sciencedirect.com/science/article/pii/S2589004223014384DiseaseBiological sciencesCell biology |
| spellingShingle | Samantha N. Thomas Brian F. Niemeyer Rocio J. Jimenez-Valdes Alexander J. Kaiser Joaquin M. Espinosa Kelly D. Sullivan Andrew Goodspeed James C. Costello Jonathan K. Alder Rodrigo Cañas-Arranz Adolfo García-Sastre Kambez H. Benam Down syndrome is associated with altered frequency and functioning of tracheal multiciliated cells, and response to influenza virus infection iScience Disease Biological sciences Cell biology |
| title | Down syndrome is associated with altered frequency and functioning of tracheal multiciliated cells, and response to influenza virus infection |
| title_full | Down syndrome is associated with altered frequency and functioning of tracheal multiciliated cells, and response to influenza virus infection |
| title_fullStr | Down syndrome is associated with altered frequency and functioning of tracheal multiciliated cells, and response to influenza virus infection |
| title_full_unstemmed | Down syndrome is associated with altered frequency and functioning of tracheal multiciliated cells, and response to influenza virus infection |
| title_short | Down syndrome is associated with altered frequency and functioning of tracheal multiciliated cells, and response to influenza virus infection |
| title_sort | down syndrome is associated with altered frequency and functioning of tracheal multiciliated cells and response to influenza virus infection |
| topic | Disease Biological sciences Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223014384 |
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