The Invasion Plasmid Antigen J (IpaJ) from Salmonella Inhibits NF-κB Activation by Suppressing IκBα Ubiquitination.
Infect Immun
; 88(3)2020 02 20.
Article
em En
| MEDLINE
| ID: mdl-31843963
ABSTRACT
Salmonella enterica serovar Pullorum is the pathogen of pullorum disease, which leads to severe economic losses in many developing countries. In contrast to the strong inflammatory response induced by Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis, S Pullorum causes systemic infection with little inflammation. The effector proteins secreted by Salmonella often play a crucial role in modulating host signal transduction and cellular processes to the pathogen's advantage. In the present study, the invasion plasmid antigen J (IpaJ) protein specifically identified in S Pullorum was found to significantly inhibit activation of the key proinflammatory transcription factor, NF-κB, which was induced by tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and lipopolysaccharide (LPS). IpaJ inhibited the NF-κB pathway in cells infected with S Pullorum through the stabilization of IκBα. Deletion of ipaJ in S Pullorum caused a significantly increased level of ubiquitinated IκBα that was subsequently degraded by the proteasome in HeLa cells. Moreover, IpaJ was efficient in the prevention of NF-κB translocation to the nucleus and ultimately interfered with the secretion of the proinflammatory cytokines IL-1ß, IL-6, and IL-8 in infected HeLa cells. Additionally, the transformation of ipaJ into S Enteritidis decreased the secretion of proinflammatory cytokines in HeLa cells through suppression of the NF-κB pathway. The infection of chicken peripheral blood monocyte-derived macrophages (chMDM) confirmed that ipaJ-deleted S Pullorum induced a stronger expression of proinflammatory cytokines than the wild-type and complementary strains. In summary, the present study revealed that IpaJ functions as an important anti-inflammatory protein involved in S Pullorum infection through inhibition of the NF-κB pathway and the subsequent inflammatory response.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Salmonelose Animal
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NF-kappa B
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Salmonella enterica
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Ubiquitinação
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Antígenos de Bactérias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China