Metabolic heterogeneity of tissue-resident macrophages in homeostasis and during helminth infection

Graham A. Heieis (), Thiago A. Patente, Luís Almeida, Frank Vrieling, Tamar Tak, Georgia Perona-Wright, Rick M. Maizels, Rinke Stienstra and Bart Everts ()
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Graham A. Heieis: Leiden University Medical Center
Thiago A. Patente: Leiden University Medical Center
Luís Almeida: Leiden University Medical Center
Frank Vrieling: Wageningen University
Tamar Tak: Leiden University Medical Center
Georgia Perona-Wright: University of Glasgow
Rick M. Maizels: University of Glasgow
Rinke Stienstra: Wageningen University
Bart Everts: Leiden University Medical Center

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Tissue-resident macrophage populations constitute a mosaic of phenotypes, yet how their metabolic states link to the range of phenotypes and functions in vivo is still poorly defined. Here, using high-dimensional spectral flow cytometry, we observe distinct metabolic profiles between different organs and functionally link acetyl CoA carboxylase activity to efferocytotic capacity. Additionally, differences in metabolism are evident within populations from a specific site, corresponding to relative stages of macrophage maturity. Immune perturbation with intestinal helminth infection increases alternative activation and metabolic rewiring of monocyte-derived macrophage populations, while resident TIM4+ intestinal macrophages remain immunologically and metabolically hyporesponsive. Similar metabolic signatures in alternatively-activated macrophages are seen from different tissues using additional helminth models, but to different magnitudes, indicating further tissue-specific contributions to metabolic states. Thus, our high-dimensional, flow-based metabolic analyses indicates complex metabolic heterogeneity and dynamics of tissue-resident macrophage populations at homeostasis and during helminth infection.

Date: 2023
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DOI: 10.1038/s41467-023-41353-z

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