GM-CSF- and M-CSF-dependent macrophage phenotypes display differential dependence on Type I interferon signaling
Abstract
M-CSF and GM-CSF are mediators involved in regulating the numbers and function of macrophage lineage populations and have been shown to contribute to macrophage heterogeneity. Type I IFN is an important mediator produced by macrophages and can have profound regulatory effects on their properties. In this study, we compared bone marrow-derived macrophages (BMM) and GM-CSF-induced BMM (GM-BMM) from wild-type and IFNAR1(-/-) mice to assess the contribution of endogenous type I IFN to the phenotypic differences between BMM and GM-BMM. BMM were capable of higher constitutive IFN-beta production, which contributed significantly to their basal transcriptome. Microarray analysis found that of the endogenous type I IFN-regulated genes specific to either BMM or GM-BMM, 488 of these gene alterations were unique to BMM, while only 50 were unique to GM-BMM. Moreover, BMM displayed enhanced basal mRNA levels, relative to GM-BMM, of a number of genes identified as being dependent on type I IFN signaling, including Stat1, Stat2, Irf7, Ccl5, Ccl12, and Cxcl10. As a result of prior type I IFN "priming," upon LPS stimulation BMM displayed increased activation of the MyD88-independent IRF-3/STAT1 pathways compared with GM-BMM, which correlated with the distinct cytokine/chemokine profiles of the two macrophage subsets. Furthermore, the autocrine type I IFN signaling loop regulated the production of the M1 and M2 signature cytokines, IL-12p70 and IL-10. Collectively, these findings demonstrate th…
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M2 macrophages can be generated under conditions of MCSF stimulation in vitro.
“we took advantage of the reports that M2 macrophages can be generated under conditions of MCSF stimulation in vitro [39], [40].”
From Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo (2014) · cites this paper as [39]
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- Authors
- Fleetwood, A. J., Dinh, H., Cook, A. D., Hertzog, P. J., & Hamilton, J. A.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Corresponding author
- Hamilton, John A
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-04-30
- Volume
- 86
- Issue
- 2
- Pages
- 411-421
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2143766145
- Cited by
- 312
- References
- 5
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 7 · 2023: 13 · 2022: 14 · 2021: 16 · 2020: 19 · 2019: 11 · 2018: 22 · 2017: 25 · 2016: 26 · 2015: 23 · 2014: 32 · 2013: 21 · 2012: 21
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Senior Principal Research Fellowship
- National Health and Medical Research Council of Australia
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- type I interferon signaling, GM-CSF, macrophage colony-stimulating factor, macrophage heterogeneity, bone marrow-derived macrophages, IFNAR1, interferon-beta, MyD88-independent signaling, lipopolysaccharide stimulation, macrophage polarization, IL-12p70, IL-10, chemokine expression, STAT1, STAT2, IRF7
- MeSH terms
- Animals, Cells, Cultured, Female, Gene Expression Regulation, Interferon Type I, Macrophages, Mice, Inbred C57BL, Phenotype, RNA, Messenger, Transcription Factors, Signal Transduction, Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, Interferon-beta, Mice, Knockout, Cell Lineage, Receptors, Chemokine, Autocrine Communication, Oligonucleotide Array Sequence Analysis, Interferon Regulatory Factor-3, Mice, Receptor, Interferon alpha-beta
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