The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition

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Date
2012Author
Version
Acceso abierto / Sarbide irekia
Type
Artículo / Artikulua
Version
Versión publicada / Argitaratu den bertsioa
Project Identifier
Impact
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10.1371/journal.ppat.1002675
Abstract
Innate 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 ...
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Innate 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. [--]
Subject
Rough vaccines,
Mutants,
O-polysaccharide,
Parasitology,
Virology,
Virulence,
Dendritic cell,
Maturation,
Cationic peptides,
Lipid-A,
Gene,
Microbiology,
Cutting edge,
Polysaccharide synthesis
Publisher
Public Library of Science
Published in
PLoS pathogens, 2012, 8(5): e1002675
Departament
Universidad Pública de Navarra/Nafarroako Unibertsitate Publikoa. IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua
Publisher version
Sponsorship
This 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.
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