The Salmonella pathogenicity island-2 subverts human NLRP3 and NLRC4 inflammasome responses.
J Leukoc Biol
; 105(2): 401-410, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30368901
ABSTRACT
Inflammasomes are signaling hubs that activate inflammatory caspases to drive cytokine maturation and cell lysis. Inflammasome activation by Salmonella Typhimurium infection or Salmonella-derived molecules is extensively studied in murine myeloid cells. Salmonella-induced inflammasome signaling in human innate immune cells, is however, poorly characterized. Here, we show that Salmonella mutation to inactivate the Salmonella pathogenicity island-2 type III secretion system (SPI2 T3SS) potentiates S. Typhimurium-induced inflammasome responses from primary human macrophages, resulting in strong IL-1ß production and macrophage death. Inactivation of the SPI1 T3SS diminished human macrophage responses to WT and ΔSPI2 Salmonella. Salmonella ΔSPI2 elicited a mixed inflammasome response from human myeloid cells, in which NLR family CARD-domain containing protein 4 (NLRC4) and NLR family PYRIN-domain containing protein 3 (NLRP3) perform somewhat redundant functions in generating IL-1ß and inducing pyroptosis. Our data suggest that Salmonella employs the SPI2 T3SS to subvert SPI1-induced NLRP3 and NLRC4 inflammasome responses in human primary macrophages, in a species-specific immune evasion mechanism.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Salmonella typhimurium
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Proteínas de Ligação ao Cálcio
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Ilhas Genômicas
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Proteínas Adaptadoras de Sinalização CARD
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Inflamassomos
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Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Austrália