The NLRP3 inflammasome complex is assembled in response to pathogens or sterile insults and is involved in generating the proinflammatory cytokines interleukin 1 (IL-1) and IL-18. In the Journal of Clinical Investigation, Kanneganti and colleagues investigate the role of the NLRP3 inflammasome in response to infection with Leishmania major, a protozoan parasite whose control depends critically on T helper type 1 (TH1) cells. Mice deficient in a functional NLRP3 inflammasome develop a lower parasite burden after cutaneous infection. The resistance of mice with a dysfunctional NLRP3 inflammasome is associated with diminished TH2 responses but enhanced TH1 responses. IL-18 is known to augment production of the signature TH1 cytokine interferon-γ, but unexpectedly, in this model of L. major infection, IL-18 instead supports the development of TH2 cells. Accordingly, neutralization of IL-18 diminishes the L. major burden. In contrast, IL-1 seems to serve no role in modulating the TH1-versus-TH2 balance in this model

J. Clin. Invest. (17 February 2015) doi:10.1172/JCI79526