Leishmania Lipophosphoglycan Triggers Caspase-11 and the Non-canonical Activation of the NLRP3 Inflammasome

Autor(es):Mostrar menos -

de Carvalho, Renan V. H. ^[1] ; Andrade, Warrison A. ^[1] ; Lima-Junior, Djalma S. ^[1] ; Dilucca, Marisa ^[1] ; de Oliveira, V, Caroline ; Wang, Kun ^[2] ; Nogueira, Paula M. ^[3] ; Rugani, Jeronimo N. ^[3] ; Soares, Rodrigo P. ^[3] ; Beverley, Stephen M. ^[4] ; Shao, Feng ^[2] ; Zamboni, Dario S. ^[5]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Ribeirao Preto, SP - Brazil

^[2] Natl Inst Biol Sci, Beijing 102206 - Peoples R China

^[3] Fundacao Oswaldo Cruz FIOCRUZ, Inst Rene Rachou, Belo Horizonte, MG - Brazil

^[4] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 - USA

^[5] de Oliveira, Caroline, V, Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CELL REPORTS; v. 26, n. 2, p. 429+, JAN 8 2019.
• Citações Web of Science: 12

Resumo

Activation of the NLRP3 inflammasome by Leishmania parasites is critical for the outcome of leishmaniasis, a disease that affects millions of people worldwide. We investigate the mechanisms involved in NLRP3 activation and demonstrate that caspase-11 (CASP11) is activated in response to infection by Leishmania species and triggers the non-canonical activation of NLRP3. This process accounts for host resistance to infection in macrophages and in vivo. We identify the parasite membrane glycoconjugate lipophosphoglycan (LPG) as the molecule involved in CASP11 activation. Cytosolic delivery of LPG in macrophages triggers CASP11 activation, and infections performed with Lpg1(-/-) parasites reduce CASP11/NLRP3 activation. Unlike bacterial LPS, purified LPG does not activate mouse CASP11 (or human Casp4) in vitro, suggesting the participation of additional molecules for LPG-mediated CASP11 activation. Our data identify a parasite molecule involved in CASP11 activation, thereby establishing the mechanisms underlying inflammasome activation in response to Leishmania species. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: 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
• Modalidade de apoio: Auxílio à Pesquisa - Temático