TY - JOUR AU - Gurung, Prajwal AU - Karki, Rajendra AU - Vogel, Peter AU - Watanabe, Makiko AU - Bix, Mark AU - Lamkanfi, Mohamed AU - Kanneganti, Thirumala-Devi T1 - An NLRP3 inflammasome–triggered Th2-biased adaptive immune response promotes leishmaniasis PY - 2015/03/02/ AB - Leishmaniasis is a major tropical disease that can present with cutaneous, mucocutaneous, or visceral manifestation and affects millions of individuals, causing substantial morbidity and mortality in third-world countries. The development of a Th1-adaptive immune response is associated with resistance to developing Leishmania major (L. major) infection. Inflammasomes are key components of the innate immune system that contribute to host defense against bacterial and viral pathogens; however, their role in regulating adaptive immunity during infection with protozoan parasites is less studied. Here, we demonstrated that the NLRP3 inflammasome balances Th1/Th2 responses during leishmaniasis. Mice lacking the inflammasome components NLRP3, ASC, or caspase 1 on a Leishmania-susceptible BALB/c background exhibited defective IL-1β and IL-18 production at the infection site and were resistant to cutaneous L. major infection. Moreover, we determined that production of IL-18 propagates disease in susceptible BALB/c mice by promoting the Th2 cytokine IL-4, and neutralization of IL-18 in these animals reduced L. major titers and footpad swelling. In conclusion, our results indicate that activation of the NLRP3 inflammasome is detrimental during leishmaniasis and suggest that IL-18 neutralization has potential as a therapeutic strategy to treat leishmaniasis patients. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI79526 VL - 125 IS - 3 UR - https://doi.org/10.1172/JCI79526 SP - 1329 EP - 1338 PB - The American Society for Clinical Investigation ER -