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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/106555
The nuclear receptor LXR limits bacterial infection of host macrophages through a mechanism that impacts cellular NAD metabolism
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Macrophages exert potent effector functions against invading microorganisms but constitute, paradoxically, a preferential niche for many bacterial strains to replicate. Using a model of infection by Salmonella Typhimurium, we have identified a molecular mechanism regulated by the nuclear receptor LXR that limits infection of host macrophages through transcriptional activation of the multifunctional enzyme CD38. LXR agonists reduced the intracellular levels of NAD+ in a CD38-dependent manner, counteracting pathogen-induced changes in macrophage morphology and the distribution of the F-actin cytoskeleton and reducing the capability of nonopsonized Salmonella to infect macrophages. Remarkably, pharmacological treatment with an LXR agonist ameliorated clinical signs associated with Salmonella infection in vivo, and these effects were dependent on CD38 expression in bonemarrow- derived cells. Altogether, this work reveals an unappreciated role for CD38 in bacterial-host cell interaction that can be pharmacologically exploited by activation of the LXR pathway.
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MATALONGA, Jonathan, GLARÍA PERCAZ, Estibaliz, BRESQUE, Mariana, ESCANDE, Carlos, CARBÓ, José m., KIEFER, Kerstin, VICENTE GARCÍA, Rubén, LEÓN MORENO, Theresa elizabeth, BECEIRO, Susana, PASCUAL GARCÍA, Mónica, SERRET, Joan, SANJURJO BOUZA, Lucía, MORÓN-ROS, Samantha, RIERA I ESCALÉ, Antoni, PAYTUBI CASABONA, Sònia, JUÁREZ GIMÉNEZ, Antonio, SOTILLO RODRÍGUEZ, Fernando, LINDBOM, Lennart, CAELLES FRANCH, Carme, SARRIAS FORNÉS, Maria rosa, SANCHO, Jaime, CASTRILLO, Antonio, CHINI, Eduardo n., VALLEDOR FERNÁNDEZ, Annabel. The nuclear receptor LXR limits bacterial infection of host macrophages through a mechanism that impacts cellular NAD metabolism. _Cell Reports_. 2017. Vol. 18, núm. 1241-1255. [consulta: 24 de gener de 2026]. ISSN: 2211-1247. [Disponible a: https://hdl.handle.net/2445/106555]