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

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

Conde Álvarez, R. et al.

Saved in:
Bibliographic Details
Main Authors: Conde Álvarez, Raquel, Grilló, María Jesús, Llobet Brossa, Enrique, Bengoechea, José Antonio, Gorvel, Jean P
Format: artículo biblioteca
Language:English
Published: Public Library of Science 2012-05-10
Online Access:http://hdl.handle.net/10261/89257
Tags: Add Tag
No Tags, Be the first to tag this record!
id dig-idab-es-10261-89257
record_format koha
spelling dig-idab-es-10261-892572021-12-28T16:16:30Z The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition Conde Álvarez, Raquel Grilló, María Jesús Grilló, María Jesús Llobet Brossa, Enrique Bengoechea, José Antonio Gorvel, Jean P Conde Álvarez, R. et al. 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. © 2012 Conde-Álvarez et al. 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 Nº 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 referen ce 2010020113. Peer reviewed 2014-01-10T11:54:17Z 2014-01-10T11:54:17Z 2012-05-10 artículo http://purl.org/coar/resource_type/c_6501 PLoS Pathogens 8(5): 1002675 (2012) 1553-7366 http://hdl.handle.net/10261/89257 10.1371/journal.ppat.1002675 1553-7374 22589715 en Publisher’s version http://dx.doi.org/10.1371/journal.ppat.1002675 open Public Library of Science
institution IDAB ES
collection DSpace
country España
countrycode ES
component Bibliográfico
access En linea
databasecode dig-idab-es
tag biblioteca
region Europa del Sur
libraryname Biblioteca del IDAB España
language English
description Conde Álvarez, R. et al.
format artículo
author Conde Álvarez, Raquel
Grilló, María Jesús
Grilló, María Jesús
Llobet Brossa, Enrique
Bengoechea, José Antonio
Gorvel, Jean P
spellingShingle Conde Álvarez, Raquel
Grilló, María Jesús
Grilló, María Jesús
Llobet Brossa, Enrique
Bengoechea, José Antonio
Gorvel, Jean P
The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition
author_facet Conde Álvarez, Raquel
Grilló, María Jesús
Grilló, María Jesús
Llobet Brossa, Enrique
Bengoechea, José Antonio
Gorvel, Jean P
author_sort Conde Álvarez, Raquel
title The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition
title_short The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition
title_full The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition
title_fullStr The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition
title_full_unstemmed The lipopolysaccharide core of Brucella abortus acts as a shield against innate immunity recognition
title_sort lipopolysaccharide core of brucella abortus acts as a shield against innate immunity recognition
publisher Public Library of Science
publishDate 2012-05-10
url http://hdl.handle.net/10261/89257
work_keys_str_mv AT condealvarezraquel thelipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT grillomariajesus thelipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT grillomariajesus thelipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT llobetbrossaenrique thelipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT bengoecheajoseantonio thelipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT gorveljeanp thelipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT condealvarezraquel lipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT grillomariajesus lipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT grillomariajesus lipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT llobetbrossaenrique lipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT bengoecheajoseantonio lipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
AT gorveljeanp lipopolysaccharidecoreofbrucellaabortusactsasashieldagainstinnateimmunityrecognition
_version_ 1777663431631962112

Similar Items