Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/40186
Title: The nuclear receptor LXR limits bacterial infection of host macrophages through a mechanism that impacts cellular NAD metabolism
Authors: Matalonga, J.
Glaria, E.
Bresque, M.
Escande, C.
Carbó, J.M.
Kiefer, K.
Vicente, R.
León, Theresa E.
Beceiro, Susana 
Pascual-García, M.
Serret, J.
Sanjurjo, L.
Morón-Ros, S.
Riera, A.
Paytubi, S.
Juarez, A.
Sotillo, F.
Lindbom, L.
Caelles, C.
Sarrias, M. R.
Sancho, J.
Castrillo Viguera, Antonio 
Chini, E. N.
Valledor, Annabel F.
UNESCO Clasification: 32 Ciencias médicas
Keywords: Bacterial infection
CD38
Cytoskeleton
LXR
Macrophage, et al
Issue Date: 2017
Journal: Cell Reports 
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 non-opsonized 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 bone-marrow-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.
URI: http://hdl.handle.net/10553/40186
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2017.01.007
Source: Cell Reports [ISSN 2211-1247], v. 18 (5), p. 1241-1255
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