The Lipopolysaccharide Core of Brucella abortus Acts as a Shield Against Innate Immunity Recognition

PLoS Pathogens

María-Jesús Grilló¹  Roman Jerala¹  Maite Iriarte¹  Kristine von Bargen²  Esteban Chaves-Olarte²  Enrique Llobet³  Elías Barquero-Calvo³  Vilma Arce-Gorvel⁴  José A. Bengoechea⁵  Raquel Conde-Álvarez⁶  Mateja Manček-Keber⁶  Carlos Chacón-Díaz⁶  Klaus Brandenburg⁷  Edgardo Moreno⁸  Ignacio Moriyón⁸  Anna Martirosyan⁹  Leyre Palacios-Chaves⁹  Jean-Pierre Gorvel⁹ 

[1] Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille University UM2 Marseille France, Institut National de la Santé et de la Recherche Médicale (INSERM) U1104 Marseille France, Centre National de la Recherche Scientifique (CNRS) UMR7280 Marseille France;Centro de Investigación en Enfermedades Tropicales, Universidad de Costa Rica, San José, Costa Rica;Department of Biotechnology, National Institute of Chemistry, Hajdrihova, Ljubljana, Slovenia;Focal Area Infection Biology, Biozentrum of the University of Basel, Basel, Switzerland;Forschungzentrum Borstel, Borstel, Germany;Institute for Tropical Health and Departamento de Microbiología y Parasitología, Universidad de Navarra, Pamplona, Spain;Instituto de Agrobiotecnología CSIC-UPNA-Gobierno de Navarra, Pamplona, Spain;Laboratory Microbial Patogénesis, Fundación Investigación Sanitaria Illes Balears-CSIC, Bunyola, Spain;Programa de Investigación en Enfermedades Tropicales, Escuela de Medicina Veterinaria, Universidad Nacional, Heredia, Costa Rica

关键词: Brucella;    Dendritic cells;    Lipids;    Enzyme-linked immunoassays;    Cytokines;    Lipid structure;    Innate immune system;    Intracellular pathogens;   

DOI  :  10.1371/journal.ppat.1002675

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY