Inhibition of Nuclear Transport of NF-ĸB p65 by the Salmonella Type III Secretion System Effector SpvD

PLoS Pathogens

Grzegorz Grabe¹  Aindrias Ryan¹  Sophie A. Matthews¹  Nathalie Rolhion¹  David W. Holden¹  Mei Liu¹  R. Christopher D. Furniss¹ 

[1] Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom

关键词: Salmonellosis;    HeLa cells;    Salmonella;    Macrophages;    Immunoblotting;    Small interfering RNAs;    Luciferase;    Cytokines;   

DOI  :  10.1371/journal.ppat.1005653

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY