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Updated: Sep 6, 2025
Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages
Published on: April 20, 2018
Monocyte-derived alveolar macrophages autonomously determine severe outcome of respiratory viral infection
Fengqi Li1, Federica Piattini1, Lea Pohlmeier1
1Institute of Molecular Health Sciences, Department of Biology, ETH Zürich, Zürich, Switzerland.
Abstract:
Various lung insults can result in replacement of resident alveolar macrophages (AM) by bone marrow monocyte-derived (BMo)-AM. However, the dynamics of this process and its long-term consequences for respiratory viral infections remain unclear. Using several mouse models and a marker to unambiguously track fetal monocyte-derived (FeMo)-AM and BMo-AM, we established the kinetics and extent of replenishment and their function to recurrent influenza A virus (IAV) infection. A massive loss of FeMo-AM resulted in rapid replenishment by self-renewal of survivors, followed by the generation of BMo-AM. BMo-AM progressively outcompeted FeMo-AM over several months, and this was due to their increased glycolytic and proliferative capacity. The presence of both naïve and experienced BMo-AM conferred severe pathology to IAV infection, which was associated with a proinflammatory phenotype. Furthermore, upon aging of naïve mice, FeMo-AM were gradually replaced by BMo-AM, which contributed to IAV disease severity in a cell-autonomous manner. Together, our results suggest that the origin rather than training of AM determines long-term function to respiratory viral infection and provide an explanation for the increased severity of infection seen in the elderly.
Insights
Bone marrow monocyte-derived (BMo)-AM replace fetal monocyte-derived (FeMo)-AM in the lungs over time. This origin shift, not immune training, impacts respiratory viral infection severity, explaining worse outcomes in the elderly.
Area of Science:
- Immunology
- Respiratory Medicine
- Cell Biology
Background:
- Lung insults can lead to alveolar macrophage (AM) replacement by bone marrow monocyte-derived (BMo)-AM.
- The dynamics and long-term effects of this AM replacement on respiratory viral infections are not well understood.
Purpose of the Study:
- To investigate the kinetics and functional consequences of AM replenishment by bone marrow monocytes during recurrent influenza A virus (IAV) infection.
- To determine if the origin of AMs (fetal vs. bone marrow-derived) influences long-term respiratory health and infection outcomes.
Main Methods:
- Utilized mouse models with a specific marker to distinguish fetal monocyte-derived (FeMo)-AM from bone marrow monocyte-derived (BMo)-AM.
- Tracked AM replenishment dynamics and assessed their function during recurrent influenza A virus (IAV) infection.
- Analyzed AM glycolytic and proliferative capacity, inflammatory phenotype, and contribution to disease pathology.
Main Results:
- Massive loss of FeMo-AM triggered rapid self-renewal, followed by BMo-AM generation.
- BMo-AM progressively outcompeted FeMo-AM due to higher glycolytic and proliferative capacity.
- Presence of BMo-AM (naïve or experienced) led to severe IAV pathology and a proinflammatory phenotype.
- Aging mice showed gradual FeMo-AM replacement by BMo-AM, increasing IAV disease severity autonomously.
Conclusions:
- The origin of alveolar macrophages (AMs), rather than their training, dictates long-term function in respiratory viral infections.
- BMo-AM accumulation contributes to increased severity of IAV infections, particularly in aging populations.
- Findings offer an explanation for heightened susceptibility to respiratory infections in the elderly.
