Aging-Impaired Filamentous Actin Polymerization Signaling Reduces Alveolar Macrophage Phagocytosis of Bacteria
Open accessAbstract
In elderly patients, bacterial infection often causes severe complications and sepsis. Compared to younger patients, older patients are more susceptible to sepsis caused by respiratory infection. Macrophage (Mϕ) phagocytosis of bacteria plays a critical role in the clearance of pathogens and the initiation of immune responses. It has been suggested that Mϕ exhibit age-related functional alterations, including reduced chemotaxis, phagocytosis, antibacterial defense, and the ability to generate reactive oxygen species. However, the mechanisms behind these changes remain unclear. The present study sought to determine changes in bacterial phagocytosis in aging alveolar Mϕ (AMϕ) and the underlying mechanisms. We show that bacteria initiate cytoskeleton remodeling in AMϕ through interaction with macrophage receptor with collagenous structure (MARCO), a bacterial scavenger receptor. This remodeling, in turn, promotes enhanced cell surface expression of MARCO and bacterial phagocytosis. We further demonstrate that Rac1-GTP mediates MARCO signaling and activates actin-related protein-2/3 complex, an F-actin nucleator, thereby inducing F-actin polymerization, filopodia formation, and increased cell surface expression of MARCO, all of which are essential for the execution of bacteria phagocytosis. However, AMϕ isolated from aging mice exhibit suppressed Rac1 mRNA and protein expression, which resulted in decreases in Rac1-GTP levels and actin-related protein-2/3 activation, as well as subsequent attenuation of F-actin polymerization, filopodia formation, and cell surface expression of MARCO. As a result, bacterial phagocytosis in aging AMϕ is decreased. This study highlights a previously unidentified mechanism by which aging impairs Mϕ phagocytosis of bacteria. Targeting these pathways may improve outcomes of bacterial infection in elderly patients.
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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 [175]
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.
“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 [107]
Increased and prolonged neutrophil recruitment in the COPD lung can have devastating effects on lung parenchyma and can enhance disease severity, prolong inflammation, and cause further tissue damage.
“Increased and prolonged neutrophil recruitment in the COPD lung can have devastating effects on lung parenchyma and can enhance disease severity, prolong inflammation, and cause further tissue damage (107, 125, 126).”
From Aging and Lung Disease (2020) · cites this paper as [107]
Age-associated impairments in innate and adaptive immune responses in the lung may contribute to increased susceptibility of older persons developing an asthma exacerbation.
“Age-associated impairments in innate and adaptive immune responses in the lung may contribute to increased susceptibility of older persons developing an asthma exacerbation (3, 19, 107, 109, 110).”
From Aging and Lung Disease (2020) · cites this paper as [107]
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Inflammation and aging: signaling pathways and intervention therapies
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- Authors
- Li, Z., Jiao, Y., Fan, E. K., Scott, M. J., Li, Y., Li, S., Billiar, T. R., Wilson, M. A., Shi, X., & Fan, J.
- Affiliations
- University of Pittsburgh (US)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Li, Zhigang
- Jiao, Yang
- Li, Yuehua
- Fan, Jie
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-11-01
- Volume
- 199
- Issue
- 9
- Pages
- 3176-3186
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC5679440
- OpenAlex
- W2758169742
- Cited by
- 78
- References
- 49
- Citations by year
- 2026: 14 · 2025: 10 · 2024: 11 · 2023: 17 · 2022: 7 · 2021: 2 · 2020: 10 · 2019: 5 · 2018: 2
- FWCI
- 2.10
- 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
- U.S. Department of Veterans Affairs (I01 BX002729)
- National Heart, Lung, and Blood Institute (R56HL123882, R01HL079669, R01HL076179)
- National Institute of General Medical Sciences (R01GM102146)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- aging, alveolar macrophages, phagocytosis, bacterial infection, sepsis, MARCO, scavenger receptors, Rac1, Arp2/3 complex, F-actin polymerization, filopodia, cytoskeletal remodeling, elderly patients, innate immunity
- MeSH terms
- Aging, Animals, Humans, Male, Actin Cytoskeleton, Neuropeptides, Phagocytosis, Receptors, Immunologic, Macrophages, Alveolar, Mice, Knockout, rac1 GTP-Binding Protein, Escherichia coli K12, Mice
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