title: Inhibition of Nuclear Transport of NF-ĸB p65 by the Salmonella Type III Secretion System Effector SpvD.
abstract: Salmonella enterica replicates in macrophages through the action of effector proteins translocated across the vacuolar membrane by a type III secretion system (T3SS). Here we show that the SPI-2 T3SS effector SpvD suppresses proinflammatory immune responses. SpvD prevented activation of an NF-ĸB-dependent promoter and caused nuclear accumulation of importin-α, which is required for nuclear import of p65. SpvD interacted specifically with the exportin Xpo2, which mediates nuclear-cytoplasmic recycling of importins. We propose that interaction between SpvD and Xpo2 disrupts the normal recycling of importin-α from the nucleus, leading to a defect in nuclear translocation of p65 and inhibition of activation of NF-ĸB regulated promoters. SpvD down-regulated pro-inflammatory responses and contributed to systemic growth of bacteria in mice. This work shows that a bacterial pathogen can manipulate host cell immune responses by interfering with the nuclear transport machinery.
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rolhion
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: R Christopher D
authors.initials: RC
authors.lastname: Furniss
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Grabe
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Aindrias
authors.initials: A
authors.lastname: Ryan
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Matthews
authors.affiliation: Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Holden
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D000067996:RAW 264.7 Cells; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000378:metabolism*; D019779:Salmonella enterica / Q000276:immunology; D051996:Transcription Factor RelA / Q000378:metabolism*; D000069296:Type III Secretion Systems / Q000378:metabolism; D037521:Virulence Factors / Q000276:immunology / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C445368:SpvD protein, Salmonella enterica; D051996:Transcription Factor RelA; D000069296:Type III Secretion Systems; D037521:Virulence Factors