Leishmaniasis, a prevalent parasitic disease that causes considerable morbidity, is dampened by the production of nitric oxide (NO) by macrophages. In Nature Medicine, Zamboni and colleagues show that the NLRP3 inflammasome is activated after infection with Leishmania and is required for optimal production of NO. Live parasites trigger assembly of NLRP3 inflammasomes, caspase-1 activation and release of IL-1β, but dead parasites do not. Signaling through the IL-1β receptor via MyD88 acts in synergy with IFN-γ to enhance expression of the gene encoding inducible NO synthase and elicit NO production. Mice deficient in the inflammasome components NLRP3, Asc or caspase-1 have a greater parasite burden, similar to that of mice that lack NO synthase. It remains unclear how Leishmania parasites trigger inflammasome activation; however, it probably involves active lysosomal membrane damage triggered by the parasite.

Nat. Med. (9 June 2013) doi:10.1038/nm.3221