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Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense

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 macrop...

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Autores principales: Krejčová, Gabriela, Danielová, Adéla, Nedbalová, Pavla, Kazek, Michalina, Strych, Lukáš, Chawla, Geetanjali, Tennessen, Jason M, Lieskovská, Jaroslava, Jindra, Marek, Doležal, Tomáš, Bajgar, Adam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867711/
https://www.ncbi.nlm.nih.gov/pubmed/31609200
http://dx.doi.org/10.7554/eLife.50414
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author Krejčová, Gabriela
Danielová, Adéla
Nedbalová, Pavla
Kazek, Michalina
Strych, Lukáš
Chawla, Geetanjali
Tennessen, Jason M
Lieskovská, Jaroslava
Jindra, Marek
Doležal, Tomáš
Bajgar, Adam
author_facet Krejčová, Gabriela
Danielová, Adéla
Nedbalová, Pavla
Kazek, Michalina
Strych, Lukáš
Chawla, Geetanjali
Tennessen, Jason M
Lieskovská, Jaroslava
Jindra, Marek
Doležal, Tomáš
Bajgar, Adam
author_sort Krejčová, Gabriela
collection PubMed
description 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 adults of the 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 Hypoxia inducible factor 1α (HIF1α) and Lactate dehydrogenase (LDH) are required for macrophage activation, their bactericidal function, and resistance to infection, thus documenting the conservation of this cellular response between insects 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.
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spelling pubmed-68677112019-11-23 Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense Krejčová, Gabriela Danielová, Adéla Nedbalová, Pavla Kazek, Michalina Strych, Lukáš Chawla, Geetanjali Tennessen, Jason M Lieskovská, Jaroslava Jindra, Marek Doležal, Tomáš Bajgar, Adam eLife Immunology and Inflammation 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 adults of the 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 Hypoxia inducible factor 1α (HIF1α) and Lactate dehydrogenase (LDH) are required for macrophage activation, their bactericidal function, and resistance to infection, thus documenting the conservation of this cellular response between insects 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. eLife Sciences Publications, Ltd 2019-10-14 /pmc/articles/PMC6867711/ /pubmed/31609200 http://dx.doi.org/10.7554/eLife.50414 Text en © 2019, Krejčová et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Krejčová, Gabriela
Danielová, Adéla
Nedbalová, Pavla
Kazek, Michalina
Strych, Lukáš
Chawla, Geetanjali
Tennessen, Jason M
Lieskovská, Jaroslava
Jindra, Marek
Doležal, Tomáš
Bajgar, Adam
Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense
title Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense
title_full Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense
title_fullStr Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense
title_full_unstemmed Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense
title_short Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense
title_sort drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867711/
https://www.ncbi.nlm.nih.gov/pubmed/31609200
http://dx.doi.org/10.7554/eLife.50414
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