Inflammasome-derived IL-1 beta production induces nitric oxide-mediated resistance to Leishmania

Autor(es):Mostrar menos -

Lima-Junior, Djalma S. ^{[1, 2]} ; Costa, Diego L. ^[1] ; Carregaro, Vanessa ^[1] ; Cunha, Larissa D. ^[2] ; Silva, Alexandre L. N. ^[2] ; Mineo, Tiago W. P. ^[1] ; Gutierrez, Fredy R. S. ^[1] ; Bellio, Maria ^[3] ; Bortoluci, Karina R. ^{[4, 5]} ; Flavell, Richard A. ^{[6, 7]} ; Bozza, Marcelo T. ^[3] ; Silva, Joao S. ^[1] ; Zamboni, Dario S. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-14049 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Biol Celular Mol & Bioagentes Patogencios, BR-14049 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Rio de Janeiro, Inst Microbiol, Dept Imunol, Rio De Janeiro - Brazil

^[4] Univ Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo - Brazil

^[5] Univ Fed Sao Paulo, Ctr Terapia Celular & Mol, Sao Paulo - Brazil

^[6] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT - USA

^[7] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 - USA

• Tipo de documento: Artigo Científico
• Fonte: Nature Medicine; v. 19, n. 7, p. 909+, JUL 2013.
• Citações Web of Science: 145

Resumo

Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study we show that the Nlrp3 inflammasome is activated in response to Leishmania infection and is important for the restriction of parasite replication both in macrophages and in vivo as demonstrated through the infection of inflammasome-deficient mice with Leishmania amazonensis, Leishmania braziliensis and Leishmania infantum chagasi. Inflammasome-driven interleukin-1 beta (IL-1 beta) production facilitated host resistance to infection, as signaling through IL-1 receptor (IL-1R) and MyD88 was necessary and sufficient to trigger inducible nitric oxide synthase (NOS2)-mediated production of NO. In this manuscript we identify a major signaling platform for host resistance to Leishmania spp. infection and describe the molecular mechanisms underlying Leishmania-induced NO production. (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
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 09/05054-6 - O papel de Ipaf e caspase-1 no controle da infecção por Leishmania (Leishmania) amazonensis
• Beneficiário: Djalma de Souza Lima Júnior
• Modalidade de apoio: Bolsas no Brasil - Doutorado