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Abstract Stimulation of dendritic cells (DCs) through toll-like receptors (TLRs) is accompanied by an increased metabolic demand, which provides metabolites and energy required for DC activation. This metabolic requirement is fulfilled by TLR-driven rapid glycolytic burst, and inhibition of glycolysis impairs the survival and effector function of DCs. Although previous studies have shown an important role for extracellular glucose uptake via glucose transporter 1 (Glut1) in supporting TLR-driven glycolysis, the contributions of intracellular glucose stores to these processes have not been well-defined. While non-immune cells store glucose as glycogen, the role of glycogen in DCs has not been identified. Here, we demonstrate that cell-intrinsic glycogen metabolism in DCs supports the early glycolytic reprogramming essential for TLR activation, particularly before Glut1 upregulation. DCs express key enzymes for glycogen metabolism, possess intracellular glycogen stores, and inhibition of glycogen breakdown severely impairs the effector function of DCs, including the ability to stimulate T cells. Our preliminary data show a time-dependent increase in intracellular glycogen levels upon TLR stimulation, implying that intricate regulatory mechanisms of glycogen metabolism are at play for proper activation responses. Interestingly, our metabolomics data indicate that the glycogen metabolism in DCs generates both glycolytic and TCA cycle intermediates and that glycogen-derived carbons preferentially engage in metabolic pathways distinct from free glucose catabolism. Our work reveals a novel metabolic regulatory pathway by which DCs differentially utilize glycogen and glucose metabolism to support their activation.

The ITER project requires additional heating by two neutral beam injectors, each accelerating up to 1 MV a 40 A beam of negative deuterium ions for one hour. Such requirements have never been reached, so it was decided to build in Padova a facility (PRIMA) that hosts two experimental devices: SPIDER, a 100 kV negative H/D RF beam source, and MITICA, a full-scale injector for the ITER NBI. SPIDER has begun operation in 2018, while MITICA is expected to start after 2020. In both devices the accelerated deuterium beam impinges on an actively cooled beam dump used to stop the deuterons. Detection of fusion neutrons produced between beam–deuterons and dump-embedded deuterons will be used as a means to resolve the horizontal beam intensity profile. A neutron detection system called Close-contact Neutron Emission Surface Mapping (CNESM) is installed right behind the SPIDER beam dump, with the aim to provide the neutron emission map of the beam dump surface. The core of this diagnostic system is an nGEM (neutron-Gas Electron Multiplier) detector which will be able to reconstruct the fast neutron beam profile with an efficiency of about 10−4. A crucial point in order to correctly reconstruct the profile of the deposited D− power is the directionality discrimination capability of the detector. This paper reports on the results of the characterization of the nGEM directionality capabilities, performed at the Frascati Neutron Generator (FNG) using 2.5 MeV neutrons, before installation of the detector inside the SPIDER vacuum vessel. © 2018 Elsevier B.V.