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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 Coxiella burnetii type IV secretion system effector IcaA

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Autor(es):
Cunha, Larissa D. [1] ; Ribeiro, Juliana M. [1] ; Fernandes, Talita D. [1] ; Massis, Liliana M. [1] ; Khoo, Chen Ai [2] ; Moffatt, Jennifer H. [2] ; Newton, Hayley J. [2] ; Roy, Craig R. [3] ; Zamboni, Dario S. [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo FMRP USP, Med Sch Ribeirao Preto, Dept Cell Biol, BR-14049900 Sao Paulo - Brazil
[2] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic 3000 - Australia
[3] Yale Univ, Dept Microbial Pathogenesis, Sch Med, New Haven, CT 06536 - USA
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: NATURE COMMUNICATIONS; v. 6, DEC 2015.
Citações Web of Science: 30
Resumo

Coxiella burnetii is a highly infectious bacterium that promotes its own replication in macrophages by inhibiting several host cell responses. Here, we show that C. burnetii inhibits caspase-1 activation in primary mouse macrophages. By using co-infection experiments, we determine that the infection of macrophages with C. burnetii inhibits the caspase-11-mediated non-canonical activation of the NLRP3 inflammasome induced by subsequent infection with Escherichia coli or Legionella pneumophila. Genetic screening using flagellin mutants of L. pneumophila as a surrogate host, reveals a novel C. burnetii gene (IcaA) involved in the inhibition of caspase activation. Expression of IcaA in L. pneumophila inhibited the caspase-11 activation in macrophages. Moreover, icaA(-) mutants of C. burnetii failed to suppress the caspase-11-mediated inflammasome activation induced by L. pneumophila. Our data reveal IcaA as a novel C. burnetii effector protein that is secreted by the Dot/Icm type IV secretion system and interferes with the caspase-11-induced, non-canonical activation of the inflammasome. (AU)

Processo FAPESP: 14/50268-2 - Deciphering the interactions between Legionella longbeachae and eukaryotic host cells
Beneficiário:Dario Simões Zamboni
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
Beneficiário:Fernando de Queiroz Cunha
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 14/04684-4 - O inflamassoma na resposta contra patógenos intracelulares e os mecanismos microbianos relacionados à evasão
Beneficiário:Dario Simões Zamboni
Linha de fomento: Auxílio à Pesquisa - Temático