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Alveolar Macrophage Apoptosis Contributes to Pneumococcal Clearance in a Resolving Model of Pulmonary Infection
Open accessAbstract
The role of alveolar macrophages (AM) in host defense against pulmonary infection has been difficult to establish using in vivo models. This may reflect a reliance on models of fulminant infection. To establish a unique model of resolving infection, with which to address the function of AM, C57BL/6 mice received low-dose intratracheal administration of pneumococci. Administration of low doses of pneumococci produced a resolving model of pulmonary infection characterized by clearance of bacteria without features of pneumonia. AM depletion in this model significantly increased bacterial outgrowth in the lung. Interestingly, a significant increase in the number of apoptotic AM was noted with the low-dose infection as compared with mock infection. Caspase inhibition in this model decreased AM apoptosis and increased the number of bacteremic mice, indicating a novel role for caspase activation in pulmonary innate defense against pneumococci. These results suggest that AM play a key role in clearance of bacteria from the lung during subclinical infection and that induction of AM apoptosis contributes to the microbiologic host defense against pneumococci.
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“Among host innate immune players, resident alveolar macrophages (AMs) are considered to be the most important first line of defense against respiratory pneumococcal infections (13), through their high phagocytic capacity (14–16).”
From Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections (2013) · cites this paper as [15]
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Metadata
- Authors
- Dockrell, D. H., Marriott, H. M., Prince, L. R., Ridger, V. C., Ince, P. G., Hellewell, P. G., & Whyte, M. K. B.
- Affiliations
- University of Sheffield (GB)
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-11
- Volume
- 171
- Issue
- 10
- Pages
- 5380-5388
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1781589933
- Cited by
- 239
- References
- 68
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 4 · 2023: 11 · 2022: 9 · 2021: 11 · 2020: 15 · 2019: 13 · 2018: 9 · 2017: 12 · 2016: 12 · 2015: 18 · 2014: 18 · 2013: 12 · 2012: 10
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- alveolar macrophages, macrophage apoptosis, Streptococcus pneumoniae, asymptomatic infection, caspase activation, bacteremia, pulmonary innate immunity, host defense
- MeSH terms
- Amino Acid Chloromethyl Ketones, Animals, Cell Count, Disease Models, Animal, Dose-Response Relationship, Immunologic, Female, Immunity, Innate, Injections, Intraperitoneal, Intubation, Intratracheal, Mice, Inbred C57BL, Pneumonia, Pneumococcal, Streptococcus pneumoniae, Cysteine Proteinase Inhibitors, Up-Regulation, Bacteremia, Macrophages, Alveolar, Apoptosis, Mice, Caspase Inhibitors
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