Inflammasome-derived IL-1'beta' production induces nitric oxide-mediated resistance to Leishmania
| Autor: | Dario S. Zamboni, Fredy R. S. Gutierrez, João Santana da Silva, Maria Bellio, Marcelo T. Bozza, Djalma S. Lima-Junior, Vanessa Carregaro, Richard A. Flavell, Larissa D. Cunha, Alexandre L. N. Silva, Tiago W. P. Mineo, Diego L. Costa, Karina R. Bortoluci |
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| Rok vydání: | 2013 |
| Předmět: |
ÓXIDO NÍTRICO (IMUNOLOGIA)
Inflammasomes Interleukin-1beta Nitric Oxide Synthase Type II Nitric Oxide General Biochemistry Genetics and Molecular Biology Microbiology Nitric oxide chemistry.chemical_compound Mice In vivo parasitic diseases NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Receptor Leishmaniasis Cells Cultured Disease Resistance Leishmania Mice Knockout biology Caspase 1 Inflammasome General Medicine medicine.disease biology.organism_classification Leishmania braziliensis Nitric oxide synthase CARD Signaling Adaptor Proteins Mice Inbred C57BL Cytoskeletal Proteins chemistry Immunology biology.protein Female Apoptosis Regulatory Proteins Carrier Proteins medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | 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-1β (IL-1β) 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. |
| Databáze: | OpenAIRE |
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