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, Amalia Dolga

Research output: Contribution to journalArticleScientificpeer-review

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.

Original languageEnglish
Article number6454
JournalNature Communications
Volume14
Issue number1
Number of pages24
ISSN2041-1723
DOIs
Publication statusPublished - Dec 2023
MoE publication typeA1 Journal article-refereed

Bibliographical note

Publisher Copyright:
© 2023, Springer Nature Limited.

Fields of Science

  • 3121 General medicine, internal medicine and other clinical medicine

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