Inhibition of Nuclear Transport of NF-[kgreen]B p65 by the Salmonella Type III Secretion System Effector SpvD

• Published in: PLoS pathogens Vol. 12; no. 5
• Main Authors: Rolhion, Nathalie, Furniss, R ChristopherD, Grabe, Grzegorz, Ryan, Aindrias, Liu, Mei, Matthews, Sophie A, Holden, David W
• Format: Journal Article
• Language: English
• Published: 01.05.2016
• Subjects: Salmonella enterica
• ISSN: 1553-7374
• DOI: 10.1371/journal.ppat.1005653

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-[kgreen]B-dependent promoter and caused nuclear accumulation of importin-[alpha] , 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-[alpha] from the nucleus, leading to a defect in nuclear translocation of p65 and inhibition of activation of NF-[kgreen]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.