Cited by 239Pneumonia and Respiratory InfectionsPhagocytosis and Immune RegulationImmune Response and Inflammation

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Alveolar Macrophage Apoptosis Contributes to Pneumococcal Clearance in a Resolving Model of Pulmonary Infection

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Dockrell, David H, Marriott, Helen M, Prince, Lynne R, Ridger, Victoria C, Ince, Paul G, Hellewell, Paul G, Whyte, Moira K B·2003·The Journal of Immunology

DOI 10.4049/jimmunol.171.10.5380

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Abstract

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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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: Dockrell, David H
Marriott, Helen M
Prince, Lynne R
Ridger, Victoria C
Ince, Paul G
Hellewell, Paul G
Whyte, Moira K B
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
DOI: 10.4049/jimmunol.171.10.5380
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
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
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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Alveolar Macrophage Apoptosis Contributes to Pneumococcal Clearance in a Resolving Model of Pulmonary Infection

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