Pathogenic ubiquitination of GSDMB inhibits NK cell bactericidal functions.
Cell
; 184(12): 3178-3191.e18, 2021 06 10.
Article
em En
| MEDLINE
| ID: mdl-34022140
ABSTRACT
Gasdermin B (GSDMB) belongs to a large family of pore-forming cytolysins that execute inflammatory cell death programs. While genetic studies have linked GSDMB polymorphisms to human disease, its function in the immunological response to pathogens remains poorly understood. Here, we report a dynamic host-pathogen conflict between GSDMB and the IpaH7.8 effector protein secreted by enteroinvasive Shigella flexneri. We show that IpaH7.8 ubiquitinates and targets GSDMB for 26S proteasome destruction. This virulence strategy protects Shigella from the bacteriocidic activity of natural killer cells by suppressing granzyme-A-mediated activation of GSDMB. In contrast to the canonical function of most gasdermin family members, GSDMB does not inhibit Shigella by lysing host cells. Rather, it exhibits direct microbiocidal activity through recognition of phospholipids found on Gram-negative bacterial membranes. These findings place GSDMB as a central executioner of intracellular bacterial killing and reveal a mechanism employed by pathogens to counteract this host defense system.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Shigella flexneri
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Células Matadoras Naturais
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Biomarcadores Tumorais
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Proteínas Citotóxicas Formadoras de Poros
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Interações Hospedeiro-Patógeno
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Ubiquitinação
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Proteínas de Neoplasias
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos