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MACROPHAGES IN 2019

On macrophage diversity and inflammatory metabolic timers

Nature Reviews Immunology volume 20, pages 89–90 (2020)Cite this article

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Key papers were published in 2019 that solidify the notion that macrophage gene expression is remarkably diverse; single-cell sequencing combined with new macrophage-specific genetic tools has provided unexpected insights into the tissue-specific and inflammatory diversity of macrophages. In addition, a new mechanism of inflammatory control of macrophage diversity based on lactate-mediated histone modifications was discovered.

Key advances

  • Single-cell sequencing revealed unexpected macrophage diversity in all organs examined so far.

  • Major differences were reported in gene expression between human and mouse macrophages in the setting of lung cancer, whereas gene expression in other immune cell populations closely correlated between species.

  • New macrophage-specific Cre deleters have been developed and tested.

  • An unexpected ‘timing’ mechanism mediated by lactate seems to control macrophage inflammatory transitions.

A fundamental problem in understanding how macrophages regulate inflammation is their phenotypical and functional heterogeneity. How can we determine (and potentially target) a pathogenic or protective macrophage function if there are multiple types of macrophage in any given tissue site and if these populations temporally change their phenotypes in response to local extrinsic cues? An active wave of research has recently established that, first, tissues contain macrophages of both embryonic and bone marrow origin and that the proportions of these distinct populations can change with time, tissue niche and injury; and second, macrophages are sufficiently plastic that they can adopt tissue-specific phenotypes independent of their origin. Thus, the debate over macrophage ontogeny and development seems more or less settled when viewed from a higher perspective. However, the twin problems of dissecting macrophage phenotypical heterogeneity and specific function at a given time and place remain. Fortunately, technological innovations are finally allowing us to address these issues, and in 2019 single-cell approaches and new fate mapping tools greatly advanced our understanding of macrophage heterogeneity.

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Fig. 1: Hypothetical perspective for the lactate ‘timer’ model proposed by Zhang et al.7

References

  1. Cohen, M. et al. Lung single-cell signaling interaction map reveals basophil role in macrophage imprinting. Cell 175, 1031–1044 (2018).

    Article  CAS  Google Scholar 

  2. Zilionis, R. et al. Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species. Immunity 50, 1317–1334 (2019).

    Article  CAS  Google Scholar 

  3. Van Hove, H. et al. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. Nat. Neurosci. 22, 1021–1035 (2019).

    Article  Google Scholar 

  4. Masuda, T. et al. Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution. Nature 566, 388–392 (2019).

    Article  CAS  Google Scholar 

  5. Liu, Z. et al. Fate mapping via Ms4a3-expression history traces monocyte-derived cells. Cell 178, 1509–1525 (2019).

    Article  CAS  Google Scholar 

  6. Heung, L. J. & Hohl, T. M. Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans. PLOS Pathog. 15, e1007627 (2019).

    Article  Google Scholar 

  7. Zhang, D. et al. Metabolic regulation of gene expression by histone lactylation. Nature 574, 575–580 (2019).

    Article  CAS  Google Scholar 

  8. Kasper, L. H. et al. Conditional knockout mice reveal distinct functions for the global transcriptional coactivators CBP and p300 in T cell development. Mol. Cell Biol. 26, 789–809 (2006).

    Article  CAS  Google Scholar 

  9. Carmona-Fontaine, C. et al. Metabolic origins of spatial organization in the tumor microenvironment. Proc. Natl Acad. Sci. USA 114, 2934–2939 (2017).

    Article  CAS  Google Scholar 

  10. Colegio, O. R. et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513, 559–563 (2014).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author thanks K. C. El Kasmi (Boehringer Ingelheim) for discussions.

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  1. Max Planck Institute for Biochemistry, Martinsried, Germany

    Peter J. Murray

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  1. Peter J. Murray
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Correspondence to Peter J. Murray.

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Murray, P.J. On macrophage diversity and inflammatory metabolic timers. Nat Rev Immunol 20, 89–90 (2020). https://doi.org/10.1038/s41577-019-0260-2

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