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Extracellular adenosine modulates host-pathogen interactions through regulation of systemic metabolism during immune
1Department of Molecular Biology and Genetics, Faculty of Science, University of South Bohemia in Ceske Budejovice, Ceske Budejovice, Czech Republic.
Abstract:
Phagocytosis by hemocytes, Drosophila macrophages, is essential for resistance to Streptococcus pneumoniae in adult flies. Activated macrophages require an increased supply of energy and we show here that a systemic metabolic switch, involving the release of glucose from glycogen, is required for effective resistance to S. pneumoniae. This metabolic switch is mediated by extracellular adenosine, as evidenced by the fact that blocking adenosine signaling in the adoR mutant suppresses the systemic metabolic switch and decreases resistance to infection, while enhancing adenosine effects by lowering adenosine deaminase ADGF-A increases resistance to S. pneumoniae. Further, that ADGF-A is later expressed by immune cells during infection to regulate these effects of adenosine on the systemic metabolism and immune response. Such regulation proved to be important during chronic infection caused by Listeria monocytogenes. Lowering ADGF-A specifically in immune cells prolonged the systemic metabolic effects, leading to lower glycogen stores, and increased the intracellular load of L. monocytogenes, possibly by feeding the bacteria. An adenosine-mediated systemic metabolic switch is thus essential for effective resistance but must be regulated by ADGF-A expression from immune cells to prevent the loss of energy reserves and possibly to avoid the exploitation of energy by the pathogen.
Insights
A key metabolic switch, driven by adenosine, boosts fly immunity against bacteria. Immune cell regulation of this switch is crucial to prevent energy depletion and pathogen exploitation during infection.
Area of Science:
- Immunology
- Metabolic regulation
- Drosophila melanogaster research
Background:
- Hemocytes (Drosophila macrophages) are vital for combating Streptococcus pneumoniae.
- Immune cell activation necessitates enhanced energy supply.
Purpose of the Study:
- To investigate the role of a systemic metabolic switch in Drosophila's resistance to S. pneumoniae.
- To elucidate the involvement of extracellular adenosine and adenosine deaminase (ADGF-A) in this immune-metabolic interaction.
Main Methods:
- Analysis of adoR mutant flies to assess adenosine signaling.
- Manipulation of ADGF-A levels to observe effects on infection resistance and metabolism.
- Investigation of ADGF-A expression in immune cells during chronic Listeria monocytogenes infection.
Main Results:
- A systemic metabolic switch, releasing glucose from glycogen, is essential for S. pneumoniae resistance.
- Adenosine mediates this switch; blocking adenosine signaling impairs resistance.
- Lowering ADGF-A enhances adenosine effects, boosting resistance, but its specific immune cell expression is critical for regulation.
- Dysregulated ADGF-A in immune cells during chronic infection depletes energy reserves and aids pathogen growth.
Conclusions:
- An adenosine-mediated systemic metabolic switch is critical for effective host defense.
- Immune cell-derived ADGF-A is essential for regulating this metabolic switch, preventing energy depletion and potential pathogen exploitation.
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