The Nlrc4 Inflammasome contributes to restriction of pulmonary infection by flagellated Legionella spp. that trigger pyroptosis

Autor(es)

Pereira, Marcelo S. F. ^[1] ; Marques, Gabriel G. ^[1] ; DelLama, Jose Eduardo ^[1] ; Zamboni, Dario S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cell Biol, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 2, 2011.
• Citações Web of Science: 26

Resumo

The Nlrc4 inflammasome is triggered in response to contamination of the host cell cytoplasm with bacterial flagellin, which induces pyroptosis, a form of cell death that accounts for restriction of bacterial infections. Although induction of pyroptosis has been extensively investigated in response to Salmonella typhimurium and Legionella pneumophila, little is known regarding the role of the inflammasome for restriction of non-pneumophila Legionella species. Here, we used five species of the Legionella genus to investigate the importance of the inflammasome for restriction of bacterial infection in vivo. By infecting mice deficient for inflammasome components, we demonstrated that caspase-1 and Nlrc4, but not Asc, contribute to restriction of pulmonary infection with L. micdadei, L. bozemanii, L. gratiana, and L. rubrilucens. L. longbeachae, a non-flagellated bacterium that fails to trigger pyroptosis, was not restricted by the inflammasome and induced death in the infected mice. In contrast to L. longbeachae, flagellin mutants of L. pneumophila did not induce mice death; therefore, besides bypassing the Nlrc4 inflammasome, L. longbeachae may employ additional virulence strategies to replicate in mammalian hosts. Collectively, our data indicate that the Nlrc4 inflammasome plays an important role in host protection against opportunistic pathogenic bacteria that express flagellin. (AU)

• Processo FAPESP: 07/55852-0 - Determinação dos mecanismos efetores do sistema imune que participam do controle da infecção murina por Legionella pneumophila
• Beneficiário: Marcelo de Souza Fernandes Pereira
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/14437-6 - Reconhecimento de patógenos bacterianos por receptores intracelulares e sua importância no controle da infecção bacteriana
• Beneficiário: Gabriel Gomes Marques
• Linha de fomento: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• 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