Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense
- University of South Bohemia, Czech Republic
- Indiana University, United States
Abstract
Macrophage-mediated phagocytosis and cytokine production represent the front lines of resistance to bacterial invaders. A key feature of this pro-inflammatory response in mammals is the complex remodeling of cellular metabolism towards aerobic glycolysis. Although, the function of bactericidal macrophages is highly conserved, the metabolic remodeling of insect macrophages remains poorly understood. Here we used the adult fruit fly Drosophila melanogaster to investigate the metabolic changes that occur in macrophages during the acute and resolution phases of Streptococcus-induced sepsis. Our studies revealed that orthologs of the Hypoxia inducible factor 1α (HIF1α) and Lactate dehydrogenase (LDH) are required for macrophage activation, their bactericidal function, and resistance to infection, thus documenting conservation of this cellular response between insect and mammals. Further, we show that macrophages employing aerobic glycolysis induce changes in systemic metabolism that are necessary to meet the biosynthetic and energetic demands of their function and resistance to bacterial infection.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data have been provided for Figures 2 and 4 in the Supplement.
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Funding
Grantová Agentura České Republiky (Project 17-16406S)
- Tomáš Doležal
National Institute of General Medical Sciences (R35 MIRA 1R35GM119557)
- Jason M Tennessen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Krejčová et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense
eLife 8:e50414.
https://doi.org/10.7554/eLife.50414
