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Dumont, C.

Publications and source records attributed to Dumont, C..

3 recordsLinked to original sources

Hindbrain catecholaminergic inputs to the paraventricular thalamus scale feeding and metabolic efficiency in stress-related contexts

The regulation of food intake and energy balance relies on the dynamic integration of exteroceptive and interoceptive signals monitoring nutritional, metabolic, cognitive and emotional states. The paraventricular thalamus (PVT) is a central hub that, by integrating sensory, metabolic and emotional states, may contribute to the regulation of feeding and homeostatic/allostatic processes. However, the underlying PVT circuits remain still elusive. Here, we aimed at unraveling the role of catecholaminergic (CA) inputs to the PVT in scaling feeding and metabolic efficiency. First, using region-specific retrograde disruption of CA projections, we show that PVT CA inputs mainly arise from the hindbrain, notably the locus coeruleus (LC) and the nucleus tractus solitarius (NTS). Second, taking advantage of integrative calorimetric measurements of metabolic efficiency, we reveal that CA inputs to the PVT scale adaptive feeding and metabolic responses in environmental, behavioral, physiological and metabolic stress-like contexts. Third, we show that hindbrainTH[->]PVT inputs contribute in modulating the activity of PVT as well as lateral (LH) and dorsomedial (DMH) hypothalamic neurons. In conclusion, this study, by assessing the key role of CA inputs to the PVT in scaling homeostatic/allostatic regulations of feeding patterns, reveals the integrative and converging hindbrainTH[->]PVT paths that contribute to whole-body metabolic adaptations in stress-like contexts. Key pointsO_LIThe paraventricular thalamus (PVT) is known to receive projections from the hindbrain. Here, we confirm and further extend current knowledge on the existence of hindbrainTH[->]PVT catecholaminergic (CA) inputs, notably from the locus coeruleus (LC) and the nucleus tractus solitarius (NTS), with the NTS representing the main source. C_LIO_LIDisruption of hindbrainTH[->]PVT inputs contribute to the modulation of PVT-neurons activity. C_LIO_LIHindbrainTH[->]PVT inputs scale feeding strategies in environmental, behavioral, physiological and metabolic stress-like contexts. C_LIO_LIHindbrainTH[->]PVT inputs participate in regulating metabolic efficiency and nutrient partitioning in stress-like contexts. C_LIO_LIHindbrainTH[->]PVT, directly and/or indirectly, contribute in modulating the downstream activity of lateral (LH) and dorsomedial (DMH) hypothalamic neurons. C_LI

neuroscience↗

Activation of cGAS/STING pathway upon paramyxovirus infection

During inflammatory diseases, cancer and infection, the cGAS/STING pathway is known to recognize foreign or self-DNA in the cytosol and activate an innate immune response. Here, we report that negative-strand RNA paramyxoviruses, Nipah virus (NiV) and Measles virus (MeV), can also trigger the cGAS/STING axis. While mice deficient for MyD88, TRIF and MAVS still moderately control NiV infection when compared to WT mice, additional STING deficiency resulted in 100% lethality, suggesting synergistic roles of these pathways in host protection. Moreover, deletion of cGAS or STING resulted in decreased type-I interferon production with enhanced paramyxoviral infection in both human and murine cells. Finally, the phosphorylation and ubiquitination of STING, observed during viral infections, confirmed the activation of cGAS/STING pathway by NiV and MeV. Our data suggest that cGAS/STING activation is critical in controlling paramyxovirus infection, and possibly represent attractive targets to develop countermeasures against severe disease induced by these pathogens.

immunology↗

Reprogrammed Pteropus Bat Stem Cells Present Distinct Immune Signature And Are Highly Permissive For Henipaviruses

Bats are unique among mammals due to the ability of powered flight and exceptional longevity. They are also asymptomatic hosts for numerous viruses, including recently emerged zoonotic Henipaviruses Nipah and Hendra, which are highly pathogenic for humans and other mammals. Better understanding of how bats control viral infection requires development of relevant permissive cellular experimental models. By applying a somatic reprogramming protocol to Pteropus bat primary cells, using a novel combination of ESRRB, CDX2, and c-MYC transcription factors, we generated bat reprogrammed cells exhibiting stem cell-like characteristics and a neural stem cell-like molecular signature. These cells present a unique interferon-stimulated transcriptomic signature and both produce and respond to interferon type-I, highlighting differences between stem cells from bats and other mammals. In contrast to primary bat cells, these reprogrammed cells are highly susceptible to infection by Henipavirus, thereby enabling isolation of new bat viruses, study of virus-bat interactions, and better understanding of bat biology. Summary sentenceSomatic reprogramming provides new bat stem cells with unique immune properties and original viral permissivness

cell biology↗