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oai:recercat.cat:2445/1065552025-12-04T21:45:07Zcom_2072_1057col_2072_478917col_2072_478933

00925njm 22002777a 4500 dc Matalonga, Jonathan author Glaría Percaz, Estibaliz author Bresque, Mariana author Escande, Carlos author Carbó, José M. author Kiefer, Kerstin author Vicente García, Rubén author León Moreno, Theresa Elizabeth author Beceiro, Susana author Pascual García, Mónica author Serret, Joan author Sanjurjo Bouza, Lucía author Morón-Ros, Samantha author Riera i Escalé, Antoni author Paytubi Casabona, Sònia author Juárez Giménez, Antonio author Sotillo Rodríguez, Fernando author Lindbom, Lennart author Caelles Franch, Carme author Sarrias Fornés, Maria Rosa author Sancho, Jaime author Castrillo, Antonio author Chini, Eduardo N. author Valledor Fernández, Annabel author 2017-02-06T16:28:31Z 2017-02-06T16:28:31Z 2017-01-31 2017-02-06T16:28:31Z 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. Citosquelet Macròfags Receptors nuclears (Bioquímica) Cytoskeleton Macrophages Nuclear receptors (Biochemistry) The nuclear receptor LXR limits bacterial infection of host macrophages through a mechanism that impacts cellular NAD metabolism