Katedra molekulární biologie a genetiky
Department of molecular biology and genetics
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Adam Bajgar a Tomáš Doležal - publikace v PLoS Pathogens

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


Bajgar A, Dolezal T (2018) Extracellular adenosine modulates host-pathogen interactions through regulation of systemic metabolism during immune response in Drosophila. PLoS Pathog 14(4): e1007022.

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.

Author summary

The immune response is an energy-demanding process and a sufficient energy supply is important for resistance to pathogens. However, the systemic metabolism must be tightly regulated during an immune response since nutrients may also be exploited by the pathogen and host energy reserves are limited. Here we present how host-pathogen interaction can be influenced by extracellular adenosine. We show that adenosine regulates the allocation of energy during bacterial infections in flies and that its signal is crucial for host immunity. Furthermore, enhancing its effect may even boost host immunity during the acute phase. However, the removal of adenosine by adenosine deaminase and thus down-regulation of its effect on the energy metabolism might prevent unintended feeding of the pathogen at the expense of host energy reserves. Therefore, our work demonstrates on the one hand that immune cells usurp energy from the rest of the organism, which is crucial for the effectivity of the immune response but, on the other hand, that immune cells also regulate adenosine to prevent the negative consequences of the excessive release of energy.