Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense

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.

Article and author information

Author details

  1. Gabriela Krejčová

    Department of Molecular Biology and Genetics, University of South Bohemia, České Budějovice, Czech Republic
    For correspondence
    krejcovagabriela@seznam.cz
    Competing interests
    The authors declare that no competing interests exist.
  2. Adéla Danielová

    Department of Molecular Biology and Genetics, University of South Bohemia, České Budějovice, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  3. Pavla Nedbalová

    Department of Molecular Biology and Genetics, University of South Bohemia, České Budějovice, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  4. Michalina Kazek

    Department of Molecular Biology and Genetics, University of South Bohemia, České Budějovice, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  5. Lukáš Strych

    Department of Molecular Biology and Genetics, University of South Bohemia, České Budějovice, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  6. Geetanjali Chawla

    Department of Biology, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jason M Tennessen

    Department of Biology, Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3527-5683
  8. Jaroslava Lieskovská

    Department of Medical Biology, University of South Bohemia, České Budějovice, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  9. Marek Jindra

    Department of Molecular Biology and Genetics, University of South Bohemia, České Budějovice, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  10. Tomáš Doležal

    Department of Molecular Biology and Genetics, University of South Bohemia, České Budějovice, Czech Republic
    Competing interests
    The authors declare that no competing interests exist.
  11. Adam Bajgar

    Department of Molecular Biology and Genetics, University of South Bohemia, České Budějovice, Czech Republic
    For correspondence
    bajgaa00@prf.jcu.cz
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9721-7534

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.

Reviewing Editor

  1. Utpal Banerjee, University of California, Los Angeles, United States

Publication history

  1. Received: July 25, 2019
  2. Accepted: October 12, 2019
  3. Accepted Manuscript published: October 14, 2019 (version 1)
  4. Version of Record published: November 20, 2019 (version 2)

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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  1. Gabriela Krejčová
  2. Adéla Danielová
  3. Pavla Nedbalová
  4. Michalina Kazek
  5. Lukáš Strych
  6. Geetanjali Chawla
  7. Jason M Tennessen
  8. Jaroslava Lieskovská
  9. Marek Jindra
  10. Tomáš Doležal
  11. Adam Bajgar
(2019)
Drosophila macrophages switch to aerobic glycolysis to mount effective antibacterial defense
eLife 8:e50414.
https://doi.org/10.7554/eLife.50414

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