Trained immunity of alveolar macrophages enhances injury resolution via KLF4-MERTK-mediated efferocytosis.
Trained immunity of alveolar macrophages enhances injury resolution via KLF4-MERTK-mediated efferocytosis.
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DOI：
10.1084/jem.20221388
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发表时间：
2023-11-06
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Chakraborty et al. demonstrate that a subset of tissue-resident alveolar macrophages shows greater capacity for efferocytosis and prevents hyperinflammation following repeated pathogen challenges. These trained alveolar macrophages exhibit upregulation of the efferocytosis receptor MERTK mediated by the transcription factor KLF4. Recent studies suggest that training of innate immune cells such as tissue-resident macrophages by repeated noxious stimuli can heighten host defense responses. However, it remains unclear whether trained immunity of tissue-resident macrophages also enhances injury resolution to counterbalance the heightened inflammatory responses. Here, we studied lung-resident alveolar macrophages (AMs) prechallenged with either the bacterial endotoxin or with Pseudomonas aeruginosa and observed that these trained AMs showed greater resilience to pathogen-induced cell death. Transcriptomic analysis and functional assays showed greater capacity of trained AMs for efferocytosis of cellular debris and injury resolution. Single-cell high-dimensional mass cytometry analysis and lineage tracing demonstrated that training induces an expansion of a MERTKhiMarcohiCD163+F4/80low lung-resident AM subset with a proresolving phenotype. Reprogrammed AMs upregulated expression of the efferocytosis receptor MERTK mediated by the transcription factor KLF4. Adoptive transfer of these trained AMs restricted inflammatory lung injury in recipient mice exposed to lethal P. aeruginosa. Thus, our study has identified a subset of tissue-resident trained macrophages that prevent hyperinflammation and restore tissue homeostasis following repeated pathogen challenges.
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影响因子：
64.5
作者：
Bekkering, Siroon;Arts, Rob J. W.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
影响因子：
30.5
作者：
Aegerter, Helena;Kulikauskaite, Justina;Wack, Andreas
通讯作者：
Wack, Andreas
影响因子：
14.9
作者：
Bailey TL;Johnson J;Grant CE;Noble WS
通讯作者：
Noble WS
DOI：
10.4049/jimmunol.1601520
发表时间：
2017-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Elliott MR;Koster KM;Murphy PS
通讯作者：
Murphy PS
DOI：
10.1083/jcb.202212023
发表时间：
2023-02-06
期刊：
The Journal of cell biology
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