Regulation of human neutrophil IL-1β secretion induced by Escherichia coli O157:H7 responsible for hemolytic uremic syndrome

Shiga-toxin producing Escherichia coli (STEC) infections can cause from bloody diarrhea to Hemolytic Uremic Syndrome. The STEC intestinal infection triggers an inflammatory response that can facilitate the development of a systemic disease. We report here that neutrophils might contribute to this in...

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Detalhes bibliográficos
Autores: Sabbione, Florencia, Keitelman, Irene Angélica, Shiromizu, Carolina Maiumi, Vereertbrugghen, Alexia, Vera Aguilar, Douglas, Rubatto Birri, Paolo Nahuel, Pizzano, Manuela, Ramos, María Victoria, Fuentes, Federico, Saposnik, Lucas Martín, Cernutto, Agostina, Cassataro, Juliana, Jancic, Carolina Cristina, Galletti, Jeremías Gastón, Palermo, Marina Sandra, Trevani, Analía Silvina
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2023
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositório:CONICET Digital (CONICET)
Idioma:inglês
OAI Identifier:oai:ri.conicet.gov.ar:11336/227640
Acesso em linha:http://hdl.handle.net/11336/227640
Access Level:Acceso aberto
Palavra-chave:NEUTROPHIL
STEC
IL-1 BETA
NEUTROPHIL SERINE PROTEASES
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descrição
Resumo:Shiga-toxin producing Escherichia coli (STEC) infections can cause from bloody diarrhea to Hemolytic Uremic Syndrome. The STEC intestinal infection triggers an inflammatory response that can facilitate the development of a systemic disease. We report here that neutrophils might contribute to this inflammatory response by secreting Interleukin 1 beta (IL-1β). STEC stimulated neutrophils to release elevated levels of IL-1β through a mechanism that involved the activation of caspase-1 driven by the NLRP3-inflammasome and neutrophil serine proteases (NSPs). Noteworthy, IL-1β secretion was higher at lower multiplicities of infection. This secretory profile modulated by the bacteria:neutrophil ratio, was the consequence of a regulatory mechanism that reduced IL-1β secretion the higher were the levels of activation of both caspase-1 and NSPs, and the production of NADPH oxidase-dependent reactive oxygen species. Finally, we also found that inhibition of NSPs significantly reduced STEC-triggered IL-1β secretion without modulating the ability of neutrophils to kill the bacteria, suggesting NSPs might represent pharmacological targets to be evaluated to limit the STEC-induced intestinal inflammation.

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