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dc.creatorZhao, Y. (Yun)-
dc.creatorHanniffy, S. (Sean)-
dc.creatorArce-Gorvel, V. (Vilma)-
dc.creatorConde-Alvarez, R. (Raquel)-
dc.creatorOh, S. (SangKon)-
dc.creatorMoriyon, I. (Ignacio)-
dc.creatorMémet, S. (Sylvie)-
dc.creatorGorvel, J.P. (Jean Pierre)-
dc.identifier.citationZhao, Y. (Yun); Hanniffy, S. (Sean); Arce-Gorvel, V. (Vilma); et al. "Immunomodulatory properties of Brucella melitensis lipopolysaccharide determinants on mouse dendritic cells in vitro and in vivo". Virulence. 9 (1), 2018, 465 - 479es_ES
dc.description.abstractThe lipopolysaccharide (LPS) is a major virulence factor of Brucella, a facultative intracellular pathogenic Gram-negative bacterium. Brucella LPS exhibits a low toxicity and its atypical structure was postulated to delay the host immune response, favouring the establishment of chronic disease. Here we carried out an in-depth in vitro and in vivo characterisation of the immunomodulatory effects of Brucella LPS on different dendritic cell (DC) subpopulations. By using LPSs from bacteria that share some of Brucella LPS structural features, we demonstrated that the core component of B. melitensis wild-type (Bm-wt) LPS accounts for the low activation potential of Brucella LPS in mouse GM-CSF-derived (GM-) DCs. Contrary to the accepted dogma considering Brucella LPS a poor TLR4 agonist and DC activator, Bm-wt LPS selectively induced expression of surface activation markers and cytokine secretion from Flt3-Ligandderived (FL-) DCs in a TLR4-dependent manner. It also primed in vitro T cell proliferation by FL-DCs. In contrast, modified LPS with a defective core purified from Brucella carrying a mutated wadC gene (BmwadC), efficiently potentiated mouse and human DC activation and T cell proliferation in vitro. In vivo, Bm-wt LPS promoted scant activation of splenic DC subsets and limited recruitment of monocyte- DC like cells in the spleen, conversely to Bm-wadC LPS. Bm-wadC live bacteria drove high cytokine secretion levels in sera of infected mice. Altogether, these results illustrate the immunomodulatory properties of Brucella LPS and the enhanced DC activation ability of the wadC mutation with potential for vaccine development targeting Brucella core LPS structure.es_ES
dc.description.sponsorshipYZ was funded by the China Scholarship Council. This work was supported by Ministerio de Economıa y Competitividad 476 Y. ZHAO ET AL. Grant AGL2014-58795-C4-1-R, by the Fondation de la Recherche M edicale Grant FRM-CS and by institutional grants from the Centre National de la Recherche Scientifique and the Institut national de la Sant e et de la Recherche medicale.es_ES
dc.publisherTaylor & Francises_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/Retos Investigación: Proyectos de I+D+I (2014)/AGL2014-58795-C4-1-R/ES/BRUCELOSIS:TESTS DIAGNOSTICOS Y VACUNAS DIVA FRENTE A BRUCELLA OVIS Y BRUCELLA SUISes_ES
dc.subjectDendritic cellses_ES
dc.subjectIntracellular bacteriaes_ES
dc.subjectT cell proliferationes_ES
dc.subjectToll-like receptores_ES
dc.titleImmunomodulatory properties of Brucella melitensis lipopolysaccharide determinants on mouse dendritic cells in vitro and in vivoes_ES
dc.description.noteThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,distribution, and reproduction in any medium, provided the original work is properly cited.es_ES

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