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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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]
Total Authors: 13
Affiliation:
[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
Total Affiliations: 7
Document type: Journal article
Source: Nature Medicine; v. 19, n. 7, p. 909+, JUL 2013.
Web of Science Citations: 145
Abstract

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)

FAPESP's process: 09/05054-6 - The role of Ipaf and caspase-1 in the control of infection by Leishmania (Leishmania) amazonensis
Grantee:Djalma de Souza Lima Júnior
Support Opportunities: Scholarships in Brazil - Doctorate