Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction

Angélica María Sabogal-Guáqueta, Alejandro Marmolejo-Garza, Marina Trombetta-Lima, Asmaa Oun, Jasmijn Hunneman, Tingting Chen, Jari Koistinaho, Sarka Lehtonen, Arjan Kortholt, Justina C. Wolters, Barbara M. Bakker, Bart J. L. Eggen, Erik Boddeke and Amalia Dolga ()
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Angélica María Sabogal-Guáqueta: University of Groningen
Alejandro Marmolejo-Garza: University of Groningen
Marina Trombetta-Lima: University of Groningen
Asmaa Oun: University of Groningen
Jasmijn Hunneman: University of Groningen
Tingting Chen: University of Groningen
Jari Koistinaho: University of Eastern Finland
Sarka Lehtonen: University of Eastern Finland
Arjan Kortholt: University of Groningen
Justina C. Wolters: University of Groningen, University Medical Center Groningen
Barbara M. Bakker: University of Groningen, University Medical Center Groningen
Bart J. L. Eggen: University of Groningen, University Medical Center Groningen
Erik Boddeke: University of Groningen, University Medical Center Groningen
Amalia Dolga: University of Groningen

Nature Communications, 2023, vol. 14, issue 1, 1-24

Abstract: Abstract Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS) to glycolysis or alterations in other metabolic pathways. However, most of the experimental findings have been acquired in murine immune cells, and little is known about the metabolic reprogramming of human microglia. In this study, we investigate the transcriptomic, proteomic, and metabolic profiles of mouse and iPSC-derived human microglia challenged with the TLR4 agonist LPS. We demonstrate that both species display a metabolic shift and an overall increased glycolytic gene signature in response to LPS treatment. The metabolic reprogramming is characterized by the upregulation of hexokinases in mouse microglia and phosphofructokinases in human microglia. This study provides a direct comparison of metabolism between mouse and human microglia, highlighting the species-specific pathways involved in immunometabolism and the importance of considering these differences in translational research.

Date: 2023
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DOI: 10.1038/s41467-023-42096-7

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