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Title: The nuclear receptor LXR limits bacterial infection of host macrophages through a mechanism that impacts cellular NAD metabolism
Author: Matalonga, Jonathan
Glaria, Estibaliz
Bresque, Mariana
Escande, Carlos
Carbó, José María
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, Fernando
Lindbom, Lennart
Caelles Franch, Carme
Sarrias Fornés, Maria Rosa
Sancho, Jaime
Castrillo, Antonio
Chini, Eduardo N.
Valledor Fernández, Annabel
Keywords: Citosquelet
Receptors nuclears (Bioquímica)
Nuclear receptors (Biochemistry)
Issue Date: 31-Jan-2017
Publisher: Elsevier
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Cell Reports, 2017, vol. 18, p. 1241-1255
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ISSN: 2211-1247
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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