The Shigella Type III Secretion Effector IpaH4.5 Targets NLRP3 to Activate Inflammasome Signaling.
Front Cell Infect Microbiol
; 10: 511798, 2020.
Article
em En
| MEDLINE
| ID: mdl-33117724
ABSTRACT
Activation of the NLRP3 inflammasome requires the expression of NLRP3, which is strictly regulated by its capacity to directly recognize microbial-derived substances. Even though the involvement of caspase-1 activation in macrophages via NLRP3 and NLRC4 has been discovered, the accurate mechanisms by which Shigella infection triggers NLRP3 activation remain inadequately understood. Here, we demonstrate that IpaH4.5, a Shigella T3SS effector, triggers inflammasome activation by regulating NLRP3 expression through the E3 ubiquitin ligase activity of IpaH4.5. First, we found that IpaH4.5 interacted with NLRP3. As a result, IpaH4.5 modulated NLRP3 protein stability and inflammasome activation. Bacteria lacking IpaH4.5 had dramatically reduced ability to induce pyroptosis. Our results identify a previously unrecognized target of IpaH4.5 in the regulation of inflammasome signaling and clarify the molecular basis for the cytosolic response to the T3SS effector.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Shigella
/
Inflamassomos
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
Idioma:
En
Revista:
Front Cell Infect Microbiol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China