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dc.creatorConde Álvarez, Raqueles_ES
dc.creatorBargen, Kristine vones_ES
dc.creatorGrilló Dolset, María Jesúses_ES
dc.creatorJerala, Romanes_ES
dc.creatorBrandenburg, Klauses_ES
dc.creatorLlobet, Enriquees_ES
dc.creatorBengoechea Alonso, José Antonioes_ES
dc.creatorMoreno, Edgardoes_ES
dc.creatorMoriyón Uría, Ignacioes_ES
dc.creatorGorvel, Jean-Pierrees_ES
dc.creatorArce Gorvel, Vilmaes_ES
dc.creatorIriarte, Maitees_ES
dc.creatorMancek Keber, Matejaes_ES
dc.creatorBarquero-Calvo, Elíases_ES
dc.creatorPalacios Chaves, Leyrees_ES
dc.creatorChacón Díaz, Carloses_ES
dc.creatorChaves Olarte, Estebanes_ES
dc.creatorMartirosyan, Annaes_ES
dc.date.accessioned2014-06-20T06:37:07Z
dc.date.available2014-06-20T06:37:07Z
dc.date.issued2012
dc.identifier.issn1553-7374 (electronic)
dc.identifier.issn1553-7366 (print)
dc.identifier.other1276
dc.identifier.urihttps://hdl.handle.net/2454/10924
dc.description.abstractInnate immunity recognizes bacterial molecules bearing pathogen-associated molecular patterns to launch inflammatory responses leading to the activation of adaptive immunity. However, the lipopolysaccharide (LPS) of the gram-negative bacterium Brucella lacks a marked pathogen-associated molecular pattern, and it has been postulated that this delays the development of immunity, creating a gap that is critical for the bacterium to reach the intracellular replicative niche. We found that a B. abortus mutant in the wadC gene displayed a disrupted LPS core while keeping both the LPS O-polysaccharide and lipid A. In mice, the wadC mutant induced proinflammatory responses and was attenuated. In addition, it was sensitive to killing by non-immune serum and bactericidal peptides and did not multiply in dendritic cells being targeted to lysosomal compartments. In contrast to wild type B. abortus, the wadC mutant induced dendritic cell maturation and secretion of pro-inflammatory cytokines. All these properties were reproduced by the wadC mutant purified LPS in a TLR4-dependent manner. Moreover, the core-mutated LPS displayed an increased binding to MD-2, the TLR4 co-receptor leading to subsequent increase in intracellular signaling. Here we show that Brucella escapes recognition in early stages of infection by expressing a shield against recognition by innate immunity in its LPS core and identify a novel virulence mechanism in intracellular pathogenic gram-negative bacteria. These results also encourage for an improvement in the generation of novel bacterial vaccines.en
dc.description.sponsorshipThis work was funded by grants from the Spanish Ministerio de Ciencia y Tecnología (AGL2008-04514-C03-01 to I.M.; SAF2009-07885 to J.A.B and AGL2010-20247 to MJG), EU Grant agreement Nu 221948, FIDA, Universidad Nacional de Costa Rica; FS-Conare UNA/UCR IFEG29 Costa Rica; NeTropica P00059 and F00013-02; MICIT/CONICIT IFDG12; Fundación CRUSA-CSIC 2008CR0006 and 2010CR0005; Centre National de la Recherche Scientifique, Institut National de la Sante et de la Recherche Medicale. Cooperation between University of Navarra, PIET and CSIC has been favoured by the Collaboration Agreement reference 2010020113. Research and fellowship support for KVB from ANR 2010BLAN1308 BruTir, fellowship support for R. C.-A. and L. P.-C. from the Ministerio de Ciencia y Tecnología of Spain, Gobierno de Navarra and Friends of the University of Navarra and for A.M. from the Ministry of Education in France are gratefully acknowledged.en
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.publisherPublic Library of Scienceen
dc.relation.ispartofPLoS pathogens, 2012, 8(5): e1002675en
dc.rights© 2012 Conde-Álvarez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.subjectRough vaccinesen
dc.subjectMutantsen
dc.subjectO-polysaccharideen
dc.subjectParasitologyen
dc.subjectVirologyen
dc.subjectVirulenceen
dc.subjectDendritic cellen
dc.subjectMaturationen
dc.subjectCationic peptidesen
dc.subjectLipid-Aen
dc.subjectGeneen
dc.subjectMicrobiologyen
dc.subjectCutting edgeen
dc.subjectPolysaccharide synthesisen
dc.titleThe lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognitionen
dc.typeArtículo / Artikuluaes
dc.typeinfo:eu-repo/semantics/articleen
dc.contributor.departmentIdAB - Instituto de Agrobiotecnología / Agrobioteknologiako Institutuaes
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.identifier.doi10.1371/journal.ppat.1002675
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/221948
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/6PN/AGL2008-04514
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/6PN/SAF2009-07885
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/6PN/AGL2010-20247
dc.relation.publisherversionhttps://dx.doi.org/10.1371/journal.ppat.1002675
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernua


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© 2012 Conde-Álvarez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as © 2012 Conde-Álvarez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.