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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Inhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial dissemination

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Autor(es):
Codo, Ana Campos [1] ; Saraiva, Amanda Correia [1] ; dos Santos, Leonardo Lima [2] ; Visconde, Marina Francisco [3] ; Gales, Ana Cristina [3] ; Zamboni, Dario Simoes [2] ; Medeiros, Alexandra Ivo [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, SP - Brazil
[2] Univ Sao Paulo, Sch Med, Dept Cell & Mol Biol & Pathogen Bioagents, Ribeirao Preto, SP - Brazil
[3] Univ Fed Sao Paulo, Dept Internal Med, Escola Paulista Med, Div Infect Dis, Sao Paulo, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: CELL DEATH & DISEASE; v. 9, DEC 5 2018.
Citações Web of Science: 0
Resumo

Klebsiella pneumoniae is a Gram-negative bacterium responsible for severe cases of nosocomial pneumonia. During the infectious process, both neutrophils and monocytes migrate to the site of infection, where they carry out their effector functions and can be affected by different patterns of cell death. Our data show that clinical strains of K. pneumoniae have dissimilar mechanisms for surviving within macrophages; these mechanisms include modulation of microbicidal mediators and cell death. The A28006 strain induced high IL-1 beta production and pyroptotic cell death in macrophages; by contrast, the A54970 strain induced high IL-10 production and low IL-1 beta production by macrophages. Pyroptotic cell death induced by the A28006 strain leads to a significant increase in bacterial sensitivity to hydrogen peroxide, and efferocytosis of the pyroptotic cells results in efficient bacterial clearance both in vitro and in vivo. In addition, the A54970 strain was able to inhibit inflammasome activation and pyroptotic cell death by inducing IL-10 production. Here, for the first time, we present a K. pneumoniae strain able to inhibit inflammasome activation, leading to bacterial survival and dissemination in the host. The understanding of possible escape mechanisms is essential in the search for alternative treatments against multidrug-resistant bacteria. (AU)

Processo FAPESP: 11/17611-7 - Efeito da fagocitose de células apoptóticas por células dendríticas na diferenciação de células Th17: função de PGE2
Beneficiário:Alexandra Ivo de Medeiros
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 17/19870-6 - Efeito da fagocitose de células apoptóticas infectadas na ativação de macrófagos M1/M2
Beneficiário:Alexandra Ivo de Medeiros
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/18039-0 - Avaliação dos mecanismos de virulência e do fitness bacteriano de isolados clínicos de Klebsiella pneumoniae subsp. pneumoniae produtores de KPC-2
Beneficiário:Ana Cristina Gales
Linha de fomento: Auxílio à Pesquisa - Regular