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Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia
Sylvia Knapp1, Jaklien C Leemans, Sandrine Florquin
1Laboratory of Experimental Internal Medicine, Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands. s.knapp@amc.uva.nl
Abstract:
Alveolar macrophages (AMs) are considered major effector cells in host defense against respiratory tract infections by virtue of their potent phagocytic properties. In addition, AMs may regulate the host inflammatory response to infection by production of cytokines and by their capacity to phagocytose apoptotic polymorphonuclear cells (PMNs). To elucidate the in vivo contribution of AM to host defense against pneumococcal pneumonia, we depleted mice of AMs via pulmonary application of liposomal dichloromethylene-bisphosphonate (AM- mice) before inoculation with Streptococcus pneumoniae; control mice received saline (AM+sal) or liposomal phosphate-buffered saline (AM+lip) before bacterial inoculation. AM- mice displayed a significantly higher mortality compared with AM+ control mice, whereas bacterial clearance did not differ. Poor outcome of AM- mice was accompanied by a pronounced increase of local proinflammatory cytokine production as well as strongly elevated and prolonged pulmonary PMN accumulation. Closer examination of infiltrating PMN in AM- mice disclosed high proportions of apoptotic and secondary necrotic cells, reflecting the lack of efficient clearance mechanisms in the absence of AMs. Furthermore, caspase-3 staining showed only slightly higher activity in AM- mice, arguing against accelerated apoptosis per se. These data suggest that AMs are indispensable in the host response to pneumococcal pneumonia by means of their capacity to modulate inflammation, possibly via elimination of apoptotic PMNs.
Insights
Alveolar macrophages (AMs) are crucial for fighting pneumococcal pneumonia by clearing apoptotic neutrophils and regulating inflammation. Depleting AMs increases mortality, highlighting their essential role in host defense.
Area of Science:
- Immunology
- Respiratory Medicine
- Microbiology
Background:
- Alveolar macrophages (AMs) are key immune cells in the lungs, known for phagocytosis and cytokine production.
- AMs play a role in host defense against respiratory infections and clearing apoptotic cells.
Purpose of the Study:
- To investigate the in vivo role of AMs in host defense against Streptococcus pneumoniae pneumonia.
- To determine if AM depletion affects mortality, bacterial clearance, and inflammatory responses.
Main Methods:
- Mice were depleted of AMs using liposomal dichloromethylene-bisphosphonate.
- Control groups received saline or liposomal phosphate-buffered saline.
- Mice were inoculated with Streptococcus pneumoniae, and outcomes including mortality, bacterial load, cytokine levels, and neutrophil infiltration were assessed.
Main Results:
- AM-depleted mice showed significantly higher mortality compared to controls, despite similar bacterial clearance.
- Depletion of AMs led to increased local proinflammatory cytokine production and prolonged neutrophil accumulation in the lungs.
- Infiltrating neutrophils in AM-depleted mice exhibited higher rates of apoptosis and secondary necrosis, indicating impaired clearance.
Conclusions:
- AMs are indispensable for host defense against pneumococcal pneumonia.
- AMs modulate the inflammatory response, likely through the clearance of apoptotic polymorphonuclear cells (PMNs).
- Impaired apoptotic PMN clearance in AM-deficient lungs contributes to poor outcomes in pneumococcal pneumonia.