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Updated: Aug 30, 2026
Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice
Published on: March 2, 2019
Alveolar macrophage apoptosis contributes to pneumococcal clearance in a resolving model of pulmonary infection
David H Dockrell1, Helen M Marriott, Lynne R Prince
1Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Sciences, Sheffield, United Kingdom. d.h.dockrell@sheffield.ac.uk
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.
Insights
Alveolar macrophages (AM) are crucial for clearing lung infections. Inhibiting AM apoptosis during pneumococcal infection increases bacterial growth, highlighting AM
Area of Science:
- Immunology
- Pulmonary Medicine
- Microbiology
Background:
- Alveolar macrophages (AM) are critical immune cells in the lungs.
- Their precise role in host defense against pulmonary infections is not fully understood, particularly in resolving infection models.
- Existing in vivo models often focus on severe infections, potentially obscuring the function of AM in less acute scenarios.
Purpose of the Study:
- To investigate the function of alveolar macrophages (AM) in a novel model of resolving pulmonary infection.
- To elucidate the role of AM apoptosis in host defense against Streptococcus pneumoniae.
Main Methods:
- Developed a low-dose intratracheal pneumococcal infection model in C57BL/6 mice to simulate resolving infection.
- Utilized AM depletion strategies to assess their impact on bacterial clearance.
- Investigated the effect of caspase inhibition on AM apoptosis and bacterial dissemination (bacteremia).
Main Results:
- Low-dose pneumococcal infection in mice resulted in bacterial clearance without severe pneumonia, establishing a resolving infection model.
- Depletion of AM significantly enhanced bacterial outgrowth in the lungs.
- Infection led to increased apoptosis of AM, and caspase inhibition reduced this apoptosis while increasing bacteremia.
Conclusions:
- Alveolar macrophages play a significant role in clearing bacteria during subclinical pulmonary infections.
- AM apoptosis is an integral component of the host's innate immune defense against pneumococcal lung infections.
- Targeting AM apoptosis may represent a therapeutic strategy for enhancing pulmonary defense.
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