TY - JOUR
T1 - Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction
AU - Sabogal-Guáqueta, Angélica María
AU - Marmolejo-Garza, Alejandro
AU - Trombetta-Lima, Marina
AU - Oun, Asmaa
AU - Hunneman, Jasmijn
AU - Chen, Tingting
AU - Koistinaho, Jari
AU - Lehtonen, Sarka
AU - Kortholt, Arjan
AU - Wolters, Justina C
AU - Bakker, Barbara M
AU - Eggen, Bart J L
AU - Boddeke, Erik
AU - Dolga, Amalia
N1 - © 2023. Springer Nature Limited.
PY - 2023/10/13
Y1 - 2023/10/13
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-023-42096-7
DO - 10.1038/s41467-023-42096-7
M3 - Article
C2 - 37833292
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6454
ER -