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-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.
journal_name
Nat Medjournal_title
Nature medicineauthors
Lima-Junior DS,Costa DL,Carregaro V,Cunha LD,Silva AL,Mineo TW,Gutierrez FR,Bellio M,Bortoluci KR,Flavell RA,Bozza MT,Silva JS,Zamboni DSdoi
10.1038/nm.3221subject
Has Abstractpub_date
2013-07-01 00:00:00pages
909-15issue
7eissn
1078-8956issn
1546-170Xpii
nm.3221journal_volume
19pub_type
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