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Inhibition of Nuclear Transport of NF-kappa B p65 by the Salmonella Type III Secretion System Effector SpvD
Ist Teil von
PLoS pathogens, 2016-05, Vol.12 (5)
Ort / Verlag
Public Library of Science
Erscheinungsjahr
2016
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
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-kappa B-dependent promoter and caused nuclear accumulation of importin-a, 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-a from the nucleus, leading to a defect in nuclear translocation of p65 and inhibition of activation of NF-kappa B 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.