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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Active Transport, Cell Nucleus / physiology
-
Animals
-
Antigens, Bacterial / immunology
-
Antigens, Bacterial / metabolism*
-
Bacterial Proteins / immunology
-
Bacterial Proteins / metabolism*
-
Enzyme-Linked Immunosorbent Assay
-
Flow Cytometry
-
Gene Knockdown Techniques
-
HEK293 Cells
-
HeLa Cells
-
Host-Pathogen Interactions / physiology*
-
Humans
-
Immunoblotting
-
Immunoprecipitation
-
Mice
-
Microscopy, Confocal
-
Microscopy, Fluorescence
-
Oligonucleotide Array Sequence Analysis
-
Polymerase Chain Reaction
-
RAW 264.7 Cells
-
Salmonella Infections, Animal / immunology
-
Salmonella Infections, Animal / metabolism*
-
Salmonella enterica / immunology
-
Transcription Factor RelA / metabolism*
-
Type III Secretion Systems / metabolism
-
Virulence Factors / immunology
-
Virulence Factors / metabolism*
Substances
-
Antigens, Bacterial
-
Bacterial Proteins
-
SpvD protein, Salmonella enterica
-
Transcription Factor RelA
-
Type III Secretion Systems
-
Virulence Factors