Inhibition of Nuclear Transport of NF-ĸB p65 by the Salmonella Type III Secretion System Effector SpvD.
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-dep...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005653&type=printable |
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| author | Nathalie Rolhion R Christopher D Furniss Grzegorz Grabe Aindrias Ryan Mei Liu Sophie A Matthews David W Holden |
| author_facet | Nathalie Rolhion R Christopher D Furniss Grzegorz Grabe Aindrias Ryan Mei Liu Sophie A Matthews David W Holden |
| author_sort | Nathalie Rolhion |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b56fb80b5a1e43b8957b80d1b2aede65 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2016-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-b56fb80b5a1e43b8957b80d1b2aede652025-08-20T02:03:19ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-05-01125e100565310.1371/journal.ppat.1005653Inhibition of Nuclear Transport of NF-ĸB p65 by the Salmonella Type III Secretion System Effector SpvD.Nathalie RolhionR Christopher D FurnissGrzegorz GrabeAindrias RyanMei LiuSophie A MatthewsDavid W HoldenSalmonella 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005653&type=printable |
| spellingShingle | Nathalie Rolhion R Christopher D Furniss Grzegorz Grabe Aindrias Ryan Mei Liu Sophie A Matthews David W Holden Inhibition of Nuclear Transport of NF-ĸB p65 by the Salmonella Type III Secretion System Effector SpvD. PLoS Pathogens |
| title | Inhibition of Nuclear Transport of NF-ĸB p65 by the Salmonella Type III Secretion System Effector SpvD. |
| title_full | Inhibition of Nuclear Transport of NF-ĸB p65 by the Salmonella Type III Secretion System Effector SpvD. |
| title_fullStr | Inhibition of Nuclear Transport of NF-ĸB p65 by the Salmonella Type III Secretion System Effector SpvD. |
| title_full_unstemmed | Inhibition of Nuclear Transport of NF-ĸB p65 by the Salmonella Type III Secretion System Effector SpvD. |
| title_short | Inhibition of Nuclear Transport of NF-ĸB p65 by the Salmonella Type III Secretion System Effector SpvD. |
| title_sort | inhibition of nuclear transport of nf qb p65 by the salmonella type iii secretion system effector spvd |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005653&type=printable |
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