WDR90 is a new component of the NLRC4 inflammasome involved in Salmonella Typhimurium resistance.
Dev Comp Immunol
; 100: 103428, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31276698
ABSTRACT
Inflammasomes are pivotal cytosolic molecular platforms involved in infection resistance. As multiprotein complexes, they consist of NOD-like receptors (NLRs), the adaptor proteins apoptosis-associated speck-like protein containing a CARD (ASC) and the effector molecules caspase-1 and caspase-11, whose assembly and activation depends on homotypic interactions. Here we describe WD repeat containing protein 90 (WDR90) as a new inflammasome component. We found that zebrafish wdr90 is highly induced by guanylate binding protein 4 (Gbp4) independently of inflammasome activation and caspase-1 activity. This gene encodes an evolutionarily conserved protein with unknown functions that contains several WD40 domains, which are involved in coordinating multiprotein complex assembly. Functional studies in zebrafish larvae showed that forced expression of wdr90 increased caspase-1 activity and inflammasome-dependent resistance to Salmonella enterica serovar Typhimurium infection. Wdr90 acted upstream of zebrafish caspase a (Caspa), the functional homolog of mammalian caspase-1, and Asc. Reconstitution experiments of the human inflammasome in HEK293â¯cells demonstrated that WDR90 was able to physically interact with and to alter the cellular distribution of NLRC4, but not of NLRP3 and AIM2. These results highlight the complexity of the inflammasome and the interest of studying fish immunity to understand not only the evolution of the immune system but also human immunity.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Infecções por Salmonella
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Salmonella typhimurium
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Proteínas de Ligação ao Cálcio
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Proteínas do Citoesqueleto
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Proteínas de Peixe-Zebra
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Proteínas Adaptadoras de Sinalização CARD
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Inflamassomos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Dev Comp Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Espanha