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Extracellular adenosine mediates a systemic metabolic switch during immune response.

ABSTRACT: Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system. We employ the natural infection of Drosophila with a parasitoid wasp to study energy regulation during immune response. To combat the invasion, the host must produce specialized immune cells (lamellocytes) that destroy the parasitoid egg. We show that a significant portion of nutrients are allocated to differentiating lamellocytes when they would otherwise be used for development. This systemic metabolic switch is mediated by extracellular adenosine released from immune cells. The switch is crucial for an effective immune response. Preventing adenosine transport from immune cells or blocking adenosine receptor precludes the metabolic switch and the deceleration of development, dramatically reducing host resistance. Adenosine thus serves as a signal that the "selfish" immune cells send during infection to secure more energy at the expense of other tissues.

SUBMITTER: Bajgar A

PROVIDER: S-EPMC4411001 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Extracellular adenosine mediates a systemic metabolic switch during immune response.

Bajgar Adam A Kucerova Katerina K Jonatova Lucie L Tomcala Ales A Schneedorferova Ivana I Okrouhlik Jan J Dolezal Tomas T

PLoS biology 20150427 4

Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system. We employ the natural infection of Drosophila with a parasitoid wasp to study energy regulation during immune response. To combat the invasion, the host must produce specialized immune cells (lamellocytes) that destroy the parasitoid egg. We show that a significant portion of nutrients are alloca ...[more]

PMID: 25915062

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Project description:Metabolic and haemodynamic effects of adenosine were studied in antegrade and retrograde rat liver perfusions with influent nucleoside concentrations either below (i.e. 20 microM) or exceeding (i.e. 200-300 microM) the single-pass clearance capacity of the liver. Adenosine (20 microM) increased in antegrade perfusions the perfusion pressure and markedly stimulated prostaglandin D2, thromboxane B2 and glucose output, whereas in retrograde perfusions no pressure and eicosanoid response occurred and glucose output was stimulated only slightly. The perfusion-direction-dependent differences in the glucose and pressure response to adenosine (20 microM) were fully abolished in presence of ibuprofen (50 microM). When the adenosine concentration in influent was raised to 200-300 microM, i.e. to a concentration exceeding single-pass clearance of the nucleoside, the adenosine-induced prostaglandin D2 release was about 10-fold higher in retrograde perfusions than in antegrade perfusions. On the other hand, both adenosine (20-300 microM)-induced cyclic AMP (cAMP) and K+ release from the liver were not affected by the direction of perfusion, and maximal effects on cAMP release were observed at influent adenosine concentrations of 100 microM. The basal rate (adenosine absent) of prostaglandin D2 and thromboxane B2 release was about 10-fold higher in retrograde than in antegrade perfusion experiments, whereas the basal cAMP release from the liver was not affected by the direction of perfusion. Maximal adenosine-stimulated glucose output was significantly higher in antegrade than in retrograde perfusions at all adenosine concentrations tested (range 10-300 microM). Ibuprofen abolished this difference, indicating that eicosanoids liberated under the influence of adenosine contribute to the glycogenolytic response in antegrade, but not in retrograde, perfusion. Desensitization occurred following repetitive adenosine infusion; this was more pronounced for adenosine-induced prostaglandin release than for cAMP or K+ efflux. The data suggest the following. (i) Both cAMP and eicosanoids are involved in the stimulation of glycogenolysis by adenosine. (ii) Eicosanoids are probably liberated under the influence of extracellular adenosine from a portal pre-sinusoidal compartment and accordingly stimulate glycogenolysis only in antegrade perfusions. Thus signals derived from portal vein structures can modulate hepatocellular function. (iii) Contractile elements are probably located also inside the liver acinus. (iv) Eicosanoids released into the hepatic vein reflect less than 10% of hepatic eicosanoid formation, because of marked clearance by perivenous hepatocytes.

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Extracellular adenosine mediates a systemic metabolic switch during immune response.

Publications

Extracellular adenosine mediates a systemic metabolic switch during immune response.

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