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A Dectin-1-Caspase-8 Pathway Licenses Canonical Caspase-1 Inflammasome Activation and Interleukin-1ß Release in Response to a Pathogenic Fungus.
Ketelut-Carneiro, Natália; Ghosh, Sreya; Levitz, Stuart M; Fitzgerald, Katherine A; da Silva, João Santana.
Afiliação
  • Ketelut-Carneiro N; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
  • Ghosh S; Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester.
  • Levitz SM; Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester.
  • Fitzgerald KA; Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester.
  • da Silva JS; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Brazil.
J Infect Dis ; 217(2): 329-339, 2018 01 04.
Article em En | MEDLINE | ID: mdl-29099934
Background: Paracoccidioides brasiliensis is equipped with an arsenal of virulence factors that are crucial for causing infection. Our group previously defined the NLRP3 inflammasome as a mediator of P brasiliensis-induced cell damage recognition and induction of effective Th1 immune responses. However, deficiency of caspase-1 only partially reduced interleukin (IL)-1ß levels. Methods: In this study, using chemical inhibitors as well as genetically modified mice, we identify an additional pathway for IL-1ß production in response to P brasiliensis infection. Results: Paracoccidioides brasiliensis initiated caspase-8-mediated IL-1ß production, an event that was necessary for transcriptional priming and posttranslational processing of pro-IL-1ß. Caspase-8 synergizes with the canonical NLRP3 inflammasome pathway to control caspase-1 processing and IL-1ß maturation, providing a regulatory role for caspase-8 in host resistance to in vivo P brasiliensis infection. Conclusions: Taken together, these findings revealed an important role for caspase-8 in the innate immune response of host cells to P brasiliensis infection, demonstrating a connected network between noncanonical and canonical inflammasomes to coordinate IL-1ß production during fungal challenge.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Paracoccidioides / Paracoccidioidomicose / Caspase 1 / Caspase 8 / Interleucina-1beta / Inflamassomos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Infect Dis Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Paracoccidioides / Paracoccidioidomicose / Caspase 1 / Caspase 8 / Interleucina-1beta / Inflamassomos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Infect Dis Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos