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Updated: Jul 23, 2025
Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages
Published on: April 20, 2018
Th2-dependent disappearance and phenotypic conversion of mouse alveolar macrophages
Axel Dietschmann1, Andreas Ruhl1, Peter J Murray2
1Department of Infection Biology, University Hospital Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Abstract:
Alveolar macrophages (alvMs) play an important role for maintenance of lung function by constant removal of cellular debris in the alveolar space. They further contribute to defense against microbial or viral infections and limit tissue damage during acute lung injury. alvMs arise from embryonic progenitor cells, seed the alveoli before birth, and have life-long self-renewing capacity. However, recruited monocytes may also help to restore the alvM population after depletion caused by toxins or influenza virus infection. At present, the population dynamics and cellular plasticity of alvMs during allergic lung inflammation is poorly defined. To address this point, we used a mouse model of Aspergillus fumigatus-induced allergic lung inflammation and observed that Th2-derived IL-4 and IL-13 caused almost complete disappearance of alvMs. This effect required STAT6 expression in alvMs and also occurred in various other settings of type 2 immunity-mediated lung inflammation or administration of IL-4 complexes to the lung. In addition, Th2 cells promoted conversion of alvMs to alternatively activated macrophages and multinucleated giant cells. Given the well-established role of alvMs for maintenance of lung function, this process may have implications for resolution of inflammation and tissue homeostasis in allergic asthma.
Insights
Allergic lung inflammation causes alveolar macrophages (alvMs) to disappear, requiring STAT6. This study reveals how Th2 immunity impacts alvM dynamics and cellular plasticity during asthma.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Alveolar macrophages (alvMs) are crucial for lung function, clearing debris and defending against pathogens.
- While alvMs self-renew, recruited monocytes can replenish them after injury.
- The behavior of alvMs during allergic lung inflammation remains unclear.
Purpose of the Study:
- To investigate the population dynamics and cellular plasticity of alvMs in allergic lung inflammation.
- To understand the role of Th2-derived cytokines in modulating alvM behavior.
Main Methods:
- Utilized a mouse model of Aspergillus fumigatus-induced allergic lung inflammation.
- Analyzed changes in alvM populations and their differentiation.
- Investigated the requirement of STAT6 signaling in alvMs.
Main Results:
- Th2-derived IL-4 and IL-13 led to the near-complete disappearance of alvMs.
- This alvM depletion was dependent on STAT6 expression.
- Th2 cells induced the conversion of alvMs into alternatively activated macrophages and multinucleated giant cells.
- Similar effects were observed in other type 2 immunity settings and with IL-4 complex administration.
Conclusions:
- Allergic lung inflammation, driven by Th2 immunity, profoundly impacts alvM populations.
- STAT6 signaling is critical for mediating alvM disappearance in response to Th2 cytokines.
- AlvM plasticity and conversion into other cell types may affect inflammation resolution and tissue homeostasis in allergic asthma.
