Aging Impairs Alveolar Macrophage Phagocytosis and Increases Influenza-Induced Mortality in Mice
Open accessAbstract
Influenza viral infections often lead to increased mortality in older people. However, the mechanisms by which aging impacts immunity to influenza lung infection remain unclear. We employed a murine model of influenza infection to identify these mechanisms. With aging, we found reduced numbers of alveolar macrophages, cells essential for lung homeostasis. We also determined that these macrophages are critical for influenza-induced mortality with aging. Furthermore, aging vastly alters the transcriptional profile and specifically downregulates cell cycling pathways in alveolar macrophages. Aging impairs the ability of alveolar macrophages to limit lung damage during influenza infection. Moreover, aging decreases alveolar macrophage phagocytosis of apoptotic neutrophils, downregulates the scavenging receptor CD204, and induces retention of neutrophils during influenza infection. Thus, aging induces defective phagocytosis by alveolar macrophages and increases lung damage. These findings indicate that therapies that enhance the function of alveolar macrophages may improve outcomes in older people infected with respiratory viruses.
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The phagocytic capacity of pulmonary and alveolar macrophages diminishes with age, impairing the clearance of pathogens from the lungs.
“The phagocytic capacity of pulmonary and alveolar macrophages diminishes with age, impairing the clearance of pathogens from the lungs.51,174,175”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [51]
The Results section reports that alveolar macrophages in advanced-aged mice phagocytosed fewer apoptotic neutrophils than those in young mice. That supports an age-related decline in phagocytosis, but not the claimed impairment of pathogen clearance: the Discussion says transferring young macrophages into aged mice did not improve viral clearance. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThere is an age-associated decline in phagocytic capacity in alveolar and pulmonary macrophages, which results in impaired and/or delayed pathogen clearance from the lung.
“There is an age-associated decline in phagocytic capacity in alveolar and pulmonary macrophages, which results in impaired and/or delayed pathogen clearance from the lung (106–108).”
From Aging and Lung Disease (2020) · cites this paper as [108]
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References 33 · Cited by 246
- Authors
- Wong, C. K., Smith, C. A., Sakamoto, K., Kaminski, N., Koff, J. L., & Goldstein, D. R.
- Affiliations
- Yale University (US)
- University of Michigan (US)
- Corresponding author
- Goldstein, Daniel R
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-08-01
- Volume
- 199
- Issue
- 3
- Pages
- 1060-1068
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC5557035
- OpenAlex
- W2689866037
- Cited by
- 246
- References
- 33
- Citations by year
- 2026: 31 · 2025: 32 · 2024: 31 · 2023: 36 · 2022: 33 · 2021: 27 · 2020: 27 · 2019: 18 · 2018: 10 · 2017: 1
- FWCI
- 6.93
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- National Institute on Aging (K07AG050096, R01AG028082)
- National Heart, Lung, and Blood Institute (R01HL125897, R01HL130669, T32HL007853)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- aging, alveolar macrophages, phagocytosis, influenza, CD204, apoptotic neutrophils, neutrophil retention, lung injury, gene expression profiling, older adults, respiratory viral infections
- MeSH terms
- Aging, Animals, Cell Cycle, Disease Models, Animal, Humans, Influenza, Human, Lung, Neutrophils, Orthomyxoviridae Infections, Phagocytosis, Macrophages, Alveolar, Scavenger Receptors, Class A, Mice, Influenza A Virus, H1N1 Subtype
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