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Página principal > Artículos > Artículos publicados > The Nuclear Receptor LXR Limits Bacterial Infection of Host Macrophages through a Mechanism that Impacts Cellular NAD Metabolism |
Fecha: | 2017 |
Resumen: | 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. |
Ayudas: | Ministerio de Ciencia e Innovación SAF2010-14989 Ministerio de Ciencia e Innovación SAF2011-23402 Ministerio de Ciencia e Innovación SAF2014-57856 Ministerio de Ciencia e Innovación SAF2010-16725 Ministerio de Ciencia e Innovación SAF2015-71878-REDT Instituto de Salud Carlos III CPII14/00021 Ministerio de Ciencia e Innovación FPI/BES-2009-014828 Ministerio de Educación y Ciencia 2007-00821 |
Nota: | Altres ajuts: Fundació La Marató de TV3 (080930, 20134030); COST Action BM1404; ANII (INNOVA II,FCE_1_2014_1_104002, Uruguay) |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Publicado en: | Cell reports, Vol. 18, Issue 5 (January 2017) , p. 1241-1255, ISSN 2211-1247 |
16 p, 4.9 MB |