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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/50414 |
| _version_ | 1811228136276230144 |
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| author | Gabriela Krejčová Adéla Danielová Pavla Nedbalová Michalina Kazek Lukáš Strych Geetanjali Chawla Jason M Tennessen Jaroslava Lieskovská Marek Jindra Tomáš Doležal Adam Bajgar |
| author_facet | Gabriela Krejčová Adéla Danielová Pavla Nedbalová Michalina Kazek Lukáš Strych Geetanjali Chawla Jason M Tennessen Jaroslava Lieskovská Marek Jindra Tomáš Doležal Adam Bajgar |
| author_sort | Gabriela Krejčová |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T09:53:28Z |
| format | Article |
| id | doaj.art-988c82f9ff7246d7af99d3165741a2d1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:53:28Z |
| publishDate | 2019-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-988c82f9ff7246d7af99d3165741a2d12022-12-22T03:37:47ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.50414Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defenseGabriela Krejčová0Adéla Danielová1Pavla Nedbalová2Michalina Kazek3Lukáš Strych4Geetanjali Chawla5Jason M Tennessen6https://orcid.org/0000-0002-3527-5683Jaroslava Lieskovská7Marek Jindra8https://orcid.org/0000-0002-2196-9924Tomáš Doležal9https://orcid.org/0000-0001-5217-4465Adam Bajgar10https://orcid.org/0000-0002-9721-7534Department of Molecular Biology and Genetics, University of South Bohemia, Ceske Budejovice, Czech RepublicDepartment of Molecular Biology and Genetics, University of South Bohemia, Ceske Budejovice, Czech RepublicDepartment of Molecular Biology and Genetics, University of South Bohemia, Ceske Budejovice, Czech RepublicDepartment of Molecular Biology and Genetics, University of South Bohemia, Ceske Budejovice, Czech RepublicDepartment of Molecular Biology and Genetics, University of South Bohemia, Ceske Budejovice, Czech RepublicDepartment of Biology, Indiana University, Bloomington, United StatesDepartment of Biology, Indiana University, Bloomington, United StatesDepartment of Medical Biology, University of South Bohemia, Ceske Budejovice, Czech Republic; Institute of Parasitology, Biology Centre CAS, Ceske Budejovice, Czech RepublicDepartment of Molecular Biology and Genetics, University of South Bohemia, Ceske Budejovice, Czech Republic; Institute of Entomology, Biology Centre CAS, Ceske Budejovice, Czech RepublicDepartment of Molecular Biology and Genetics, University of South Bohemia, Ceske Budejovice, Czech RepublicDepartment of Molecular Biology and Genetics, University of South Bohemia, Ceske Budejovice, Czech Republic; Institute of Entomology, Biology Centre CAS, Ceske Budejovice, Czech RepublicMacrophage-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.https://elifesciences.org/articles/50414aerobic glycolysisWarburg effectpolarization of macrophagesbacterial infectionHIF1αimmunometabolism |
| spellingShingle | Gabriela Krejčová Adéla Danielová Pavla Nedbalová Michalina Kazek Lukáš Strych Geetanjali Chawla Jason M Tennessen Jaroslava Lieskovská Marek Jindra Tomáš Doležal Adam Bajgar Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense eLife aerobic glycolysis Warburg effect polarization of macrophages bacterial infection HIF1α immunometabolism |
| 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 | aerobic glycolysis Warburg effect polarization of macrophages bacterial infection HIF1α immunometabolism |
| url | https://elifesciences.org/articles/50414 |
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