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GM-CSF in the Lung Protects against Lethal Influenza Infection
Open accessAbstract
RATIONALE: Alveolar macrophages contribute to host defenses against influenza in animal models. Enhancing alveolar macrophage function may contribute to protection against influenza. OBJECTIVES: To determine if increased expression of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the lung increases resistance to influenza. METHODS: Wild-type mice and transgenic mice that expressed GM-CSF in the lung were infected with influenza virus, and lung pathology, weight loss, and mortality were measured. We also administered GM-CSF to the lungs of wild-type mice that were infected with influenza virus. MEASUREMENTS AND MAIN RESULTS: Wild-type mice all died after infection with different strains of influenza virus, but all transgenic mice expressing GM-CSF in the lungs survived. The latter also had greatly reduced weight loss and lung injury, and showed histologic evidence of a rapid host inflammatory response that controlled infection. The resistance of transgenic mice to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T cells, B cells, or neutrophils. Transgenic mice had far more alveolar macrophages than did wild-type mice, and they were more resistant to influenza-induced apoptosis. Delivery of intranasal GM-CSF to wild-type mice also conferred resistance to influenza. CONCLUSIONS: GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.
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Metadata
- Authors
- Huang, F.-F., Barnes, P. F., Feng, Y., Donis, R., Chroneos, Z. C., Idell, S., Allen, T., Perez, D. R., Whitsett, J. A., Dunussi-Joannopoulos, K., & Shams, H.
- Affiliations
- Center for Pulmonary and Infectious Disease Control
- Centers for Disease Control and Prevention, Atlanta, Georgia
- The University of Texas Health Science Center at Tyler (US)
- University of Maryland, College Park (US)
- Cincinnati Children's Hospital Medical Center (US)
- Pfizer Research, Cambridge, Massachusetts
- Corresponding author
- Shams, Homayoun
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-07
- Volume
- 184
- Issue
- 2
- Pages
- 259-268
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- PMC
- PMC6938174
- OpenAlex
- W2100796791
- Cited by
- 161
- References
- 51
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 11 · 2023: 9 · 2022: 14 · 2021: 18 · 2020: 15 · 2019: 10 · 2018: 6 · 2017: 4 · 2016: 10 · 2015: 16 · 2014: 14 · 2013: 11 · 2012: 9
- FWCI
- 8.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Flight Attendant Medical Research Institute
- Cain Foundation
- National Heart, Lung, and Blood Institute (R01HL068127)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- GM-CSF, influenza virus, alveolar macrophages, innate immunity, lung protection, transgenic mice, lung injury, apoptosis, host defense
- MeSH terms
- Administration, Intranasal, Animals, Disease Models, Animal, Flow Cytometry, Lung, Mice, Inbred C57BL, Mice, Transgenic, Orthomyxoviridae Infections, Weight Loss, Granulocyte-Macrophage Colony-Stimulating Factor, Macrophages, Alveolar, Apoptosis, Mice
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