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Macrophages

Granuloma macrophage differentiation

Nature Reviews Immunology volume 16, page 719 (2016)Cite this article

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In vitro stimulation of common macrophage and dendritic cell progenitors and macrophage precursors with M-CSF (macrophage colony-stimulating factor) and bacterial lipoprotein (BLP; a ligand for TLR2–TLR6) resulted in the formation of large multinuclear macrophages, in a manner dependent on cell-autonomous MYD88 signalling. TLR3 and TLR4 ligands were markedly less efficient at inducing multinuclear macrophages.

Using genome-wide transcriptome analysis and single-cell RNA sequencing, Herrtwich et al. showed that BLP stimulation through TLR2 drives a non-canonical macrophage differentiation programme, including the downregulation of macrophage cell fate-determining factors such as Mafb. BLP-stimulated macrophages had altered expression of genes related to cholesterol transport and metabolism, leading to lipid body accumulation, as well as increased expression of genes associated with remodelling of the extracellular matrix. Similar gene signatures were confirmed for macrophages from mycobacterial granulomas in vivo. Furthermore, in mixed bone marrow-chimeric mice infected with Mycobacterium bovis, the authors were not able to detect multinuclear macrophages containing mixed surface markers from the two bone marrow donors. Thus, it seems that multinuclear granuloma macrophages form via a distinct differentiation pathway rather than by the fusion of 'canonical' macrophages.

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References

  1. Herrtwich, L. et al. DNA damage signaling instructs polyploid macrophage fate in granulomas. Cell http://dx.doi.org/10.1016/j.cell.2016.09.054 (2016)

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Authors
  1. Kirsty Minton
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Minton, K. Granuloma macrophage differentiation. Nat Rev Immunol 16, 719 (2016). https://doi.org/10.1038/nri.2016.132

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  • DOI: https://doi.org/10.1038/nri.2016.132

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