Loss of circadian protection against influenza infection in adult mice exposed to hyperoxia as neonates
| Autor: | Katherine N. Theken, Amruta Naik, Shaon Sengupta, Mara Mermigos, Thomas G Brooks, Kaitlyn Forrest, Soon Yew Tang, Amita Sehgal, Nicholas F. Lahens, Garret A. FitzGerald, George S Worthen, Yasmine Issah |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Mouse Circadian clock medicine.disease_cause Immunology and Inflammation 0302 clinical medicine Influenza A virus Biology (General) Lung Mice Knockout Hyperoxia Microbiology and Infectious Disease General Neuroscience General Medicine respiratory system Medicine medicine.symptom influenza Research Article circadian rhythm QH301-705.5 Science neonatal lung disease Inflammation Lung injury General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Immune system Orthomyxoviridae Infections Circadian Clocks medicine Animals Circadian rhythm lung injury General Immunology and Microbiology business.industry type 2 alveolar cells medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Animals Newborn Bronchopulmonary dysplasia Alveolar Epithelial Cells Immunology hyperoxia business 030217 neurology & neurosurgery |
| Zdroj: | eLife, Vol 10 (2021) eLife |
| ISSN: | 2050-084X |
| DOI: | 10.7554/elife.61241 |
| Popis: | Adverse early-life exposures have a lasting negative impact on health. Neonatal hyperoxia that is a risk factor for bronchopulmonary dysplasia confers susceptibility to influenza A virus (IAV) infection later in life. Given our previous findings that the circadian clock protects against IAV, we asked if the long-term impact of neonatal hyperoxia vis-à-vis IAV infection includes circadian disruption. Here, we show that neonatal hyperoxia abolishes the clock-mediated time of day protection from IAV in mice, independent of viral burden through host tolerance pathways. We discovered that the lung intrinsic clock (and not the central or immune clocks) mediated this dysregulation. Loss of circadian protein, Bmal1, in alveolar type 2 (AT2) cells recapitulates the increased mortality, loss of temporal gating, and other key features of hyperoxia-exposed animals. Our data suggest a novel role for the circadian clock in AT2 cells in mediating long-term effects of early-life exposures to the lungs. |
| Databáze: | OpenAIRE |
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