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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.)

Pore Formation Triggered by Legionella spp. Is an Nlrc4 Inflammasome-Dependent Host Cell Response That Precedes Pyroptosis

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Autor(es):
Silveira, Tatiana N. ; Zamboni, Dario S. [1]
Número total de Autores: 2
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, FMRP, Med Sch Ribeirao Preto, Dept Cell Biol, BR-14049900 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: Infection and Immunity; v. 78, n. 3, p. 1403-1413, MAR 2010.
Citações Web of Science: 66
Resumo

Legionella pneumophila, the etiological agent of Legionnaires disease, is known to trigger pore formation in bone marrow-derived macrophages (BMMs) by mechanisms dependent on the type IVB secretion system known as Dot/Icm. Here, we used several mutants of L. pneumophila in combination with knockout mice to assess the host and bacterial factors involved in pore formation in BMMs. We found that regardless of Dot/Icm activity, pore formation does not occur in BMMs deficient in caspase-1 and Nlrc4/Ipaf. Pore formation was temporally associated with interleukin-1 beta secretion and preceded host cell lysis and pyroptosis. Pore-forming ability was dependent on bacterial Dot/Icm but independent of several effector proteins, multiplication, and de novo protein synthesis. Flagellin, which is known to trigger the Nlrc4 inflammasome, was required for pore formation as flaA mutant bacteria failed to induce cell permeabilization. Accordingly, transfection of purified flagellin was sufficient to trigger pore formation independent of infection. By using 11 different Legionella species, we found robust pore formation in response to L. micdadei, L. bozemanii, L. gratiana, L. jordanis, and L. rubrilucens, and this trait correlated with flagellin expression by these species. Together, the results suggest that pore formation is neither L. pneumophila specific nor the result of membrane damage induced by Dot/Icm activity; instead, it is a highly coordinated host cell response dependent on host Nlrc4 and caspase-1 and on bacterial flagellin and type IV secretion system. (AU)

Processo FAPESP: 06/52867-4 - Reconhecimento de patógenos bacterianos por receptores intracelulares e sua importância no controle da infecção microbiana
Beneficiário:Dario Simões Zamboni
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 06/55084-0 - Ativação de caspase-1 por patógenos bacterianos e sua importância no controle da infecção microbiana
Beneficiário:Tatiana Nunes Silveira
Linha de fomento: Bolsas no Brasil - Doutorado