Academic Journal
Delayed antiviral immune response in alveolar type 2 cells increases susceptibility to influenza virus in alveoli.
| Τίτλος: | Delayed antiviral immune response in alveolar type 2 cells increases susceptibility to influenza virus in alveoli. |
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| Συγγραφείς: | Shang X; Department of Basic Medicine, Tsinghua University, Beijing 100084, China., Wang Z; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China., Yu J; Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China.; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China., Zhang R; Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Liu D; Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Zou S; National Institute for Viral Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory for Medical Virology, Chinese Center for Disease Control and Prevention, Beijing 102206, China., Leung KY; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, China., Jia J; Department of Infectious Disease, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China., Fan Y; Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Chan KH; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, China., Li H; Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China.; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China., Hung IF; Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Cao B; Department of Basic Medicine, Tsinghua University, Beijing 100084, China.; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China.; Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China.; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.; Department of Pulmonary and Critical Care Medicine, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing 100029, China. |
| Πηγή: | Chinese medical journal [Chin Med J (Engl)] 2026 Sep 20; Vol. 139 (18), pp. 2780-2790. Date of Electronic Publication: 2026 Aug 10. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Chinese Medical Association ; produced by Wolters Kluwer Country of Publication: China NLM ID: 7513795 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2542-5641 (Electronic) Linking ISSN: 03666999 NLM ISO Abbreviation: Chin Med J (Engl) Subsets: MEDLINE |
| Imprint Name(s): | Publication: <2015- > : Beijing : Chinese Medical Association ; produced by Wolters Kluwer Original Publication: Peking, Chinese Medical Assn. |
| Ιατρικοί όροι (MeSH): | Alveolar Epithelial Cells*/immunology , Alveolar Epithelial Cells*/virology , Pulmonary Alveoli*/immunology , Pulmonary Alveoli*/virology, Influenza A Virus, H1N1 Subtype/pathogenicity ; Influenza A Virus, H1N1 Subtype/immunology ; Orthomyxoviridae Infections/immunology ; Virus Replication/physiology ; Animals ; Mice ; Cells, Cultured |
| Περίληψη: | Background: The alveolar sac, which serves as the primary site for gas exchange, comprises alveolar type 1 (AT1) and alveolar type 2 (AT2) cells. These epithelial cells initiate immune responses upon encountering external stimuli. However, the influenza virus infection patterns and antiviral responses exhibited by different types of alveolar epithelial cells remain understudied. This study aimed to investigate the differential susceptibility and antiviral responses of AT1 and AT2 cells during influenza virus infection. Methods: Immunofluorescence staining was performed to determine the spatial distribution of influenza A virus (IAV; H1N1). Primary murine epithelial in vitro culture models, including an AT2 sphere culture and an AT1 differentiation model, were established to elucidate the mechanisms underlying cellular susceptibility to IAV. Bulk RNA sequencing and quantitative polymerase chain reaction were performed to characterize the cellular responses to viral infection. Results: Mouse AT2 cells exhibited greater susceptibility to H1N1 than did AT1 cells. The in vitro primary epithelial cell culture models mimicked the in vivo cellular phenotype. They further reproduced the in vitro finding of relatively high viral replication in AT2 cells. Mechanistically, no significant difference was observed between AT1 and AT2 cells in the expression of α-2,3 or α-2,6 sialic acid (viral receptors). However, RNA sequencing revealed that gene ontology terms such as the response to viral infection, negative regulation of the viral life cycle, and regulation of type I interferon (IFN) production were enriched in AT1 cells. This finding was validated using quantitative polymerase chain reaction. From 12 to 48 h after infection, the expression levels of types I and III IFNs, chemokines, and IFN-stimulated genes remained lower in AT2 cells than in AT1 cells. Conclusion: Our findings indicate the localization of IAV in alveoli and highlight the vulnerability of AT2 cells, which exhibit delayed immune responses, resulting in increased viral replication. (Copyright © 2026 The Chinese Medical Association, produced by Wolters Kluwer Health, LLC. under the CC-BY-NC-ND license.) |
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| Contributed Indexing: | Keywords: AT1; AT2; Aevolar type 1; Aevolar type 2; Alveolar epithelial cells; Immune response; Influenza; RNA-sequencing |
| Entry Date(s): | Date Created: 20260810 Date Completed: 20260920 Latest Revision: 20260923 |
| Update Code: | 20260923 |
| PubMed Central ID: | PMC13593187 |
| DOI: | 10.1097/CM9.0000000000004107 |
| PMID: | 42575870 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2542-5641 |
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| DOI: | 10.1097/CM9.0000000000004107 |