Salmonella Virulence Factor SsrAB Regulated Factor Modulates Inflammatory Responses by Enhancing the Activation of NF-κB Signaling Pathway.
J Immunol
; 196(2): 792-802, 2016 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-26673132
ABSTRACT
Effector proteins encoded by Salmonella pathogenicity islands play a key role in promoting bacterial intracellular survival, colonization, and pathogenesis. In this study, we investigated the function of the virulence-associated effector SrfA (SsrAB regulated factor) both in macrophages in vitro and in infected mice in vivo. SrfA was secreted into the cytoplasm during S. Typhimurium infection and disassociated IL-1R-associated kinase-1 (IRAK-1) from the IRAK-1-Toll interacting protein (Tollip) complex by interacting with Tollip. The released IRAK-1 was phosphorylated and subsequently activated the NF-κB signaling pathway, which enhanced the LPS-induced expression of inflammatory cytokines, such as IL-8, IL-1ß, and TNF-α. The coupling of ubiquitin to endoplasmic reticulum degradation aa 183-219 domain of Tollip is the binding region for SrfA, and both the MDaa207-226 and CTaa357-377 regions of SrfA mediate binding to Tollip and NF-κB signaling activation. Deletion of SrfA in S. Typhimurium had no notable effects on its replication but impaired the induction of NF-κB activation in infected macrophages. The mice infected with srfA-deficient bacteria exhibited a decreased inflammatory response and an increased survival rate compared with those infected with wild-type S. Typhimurium. We conclude that SrfA is a novel Salmonella virulence effector that helps modulate host inflammatory responses by promoting NF-κB signaling activation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Salmonelose Animal
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Transdução de Sinais
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NF-kappa B
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Fatores de Virulência
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2016
Tipo de documento:
Article