Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila

Autor(es)

Case, Christopher L. ^[1] ; Kohler, Lara J. ^[1] ; Lima, Jonilson B. ^[2] ; Strowig, Till ^[3] ; de Zoete, Marcel R. ^[3] ; Flavell, Richard A. ^{[3, 4]} ; Zamboni, Dario S. ^[2] ; Roy, Craig R. ^[1]

Afiliação do(s) autor(es)

^[1] Yale Univ, Sch Med, Dept Microbial Pathogenesis, New Haven, CT 06536 - USA

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular Mol & Bioagentes Patogen, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 - USA

^[4] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 - USA

• Tipo de documento: Artigo Científico
• Fonte: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 110, n. 5, p. 1851-1856, JAN 29 2013.
• Citações Web of Science: 135

Resumo

A flagellin-independent caspase-1 activation pathway that does not require NAIP5 or NRLC4 is induced by the intracellular pathogen Legionella pneumophila. Here we demonstrate that this pathway requires caspase-11. Treatment of macrophages with LPS up-regulated the host components required for this caspase-11 activation pathway. Activation by Legionella differed from caspase-11 activation using previously described agonists in that Legionella caspase-11 activation was rapid and required bacteria with a functional type IV secretion system called Dot/Icm. Legionella activation of caspase-11 induced pyroptosis by a mechanism independent of the NAIP/NLRC4 and caspase-1 axis. Legionella activation of caspase-11 stimulated activation of caspase-1 through NLRP3 and ASC. Induction of caspase-11 dependent responses occurred in macrophages deficient in the adapter proteins TRIF or MyD88 but not in macrophages deficient in both signaling factors. Although caspase-11 was produced in macrophages deficient in the type-I IFN receptor, there was a severe defect in caspase-11 dependent pyroptosis in these cells. These data indicate that macrophages respond to microbial signatures to produce proteins that mediate a capsase-11 response and that the caspase-11 system provides an alternative pathway for rapid detection of an intracellular pathogen capable of evading the canonical caspase-1 activation system that responds to bacterial flagellin. (AU)

• Processo FAPESP: 12/09363-6 - Patogênese molecular e subversão das respostas do hospedeiro em infecções por Legionella spp
• Beneficiário: Dario Simões Zamboni
• Linha de fomento: Auxílio à Pesquisa - Regular
• 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: 07/53209-3 - O papel de caspase-11 na via de ativação de caspase-1 por naip5/ipaf em resposta a infecção por Legionella pneumophila
• Beneficiário: Jonilson Berlink Lima
• Linha de fomento: Bolsas no Brasil - Mestrado