Extracellular adenosine modulates host-pathogen interactions through regulation of systemic metabolism during immune response in Drosophila

• Published in: PLoS pathogens Vol. 14; no. 4; p. e1007022
• Main Authors: Bajgar, Adam, Dolezal, Tomas
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27-04-2018; Public Library of Science (PLoS)
• Subjects: Adenosine; Adenosine deaminase; Analysis; Bacterial infections; Biology and Life Sciences; Chronic infection; Dendritic cells; Dosage and administration; Drosophila; Energy; Energy reserves; Exploitation; Gene expression; Genetics; Glucose; Glycogen; Health aspects; Hemocytes; Host-parasite relationships; Host-pathogen interactions; Immune response; Immune system; Insects; Listeria; Listeria monocytogenes; Macrophages; Medicine and Health Sciences; Metabolism; Metabolites; Microbial drug resistance; Molecular biology; Pathogenesis; Pathogens; Phagocytosis; Physiological aspects; Streptococcus infections; Streptococcus pneumoniae; Czech Republic
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007022

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.