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Moreover, administering anti\u2010IL\u20101\u03b2 antibody to infected Amp B\u2013treated mice showed significantly less parasite clearance. Investigation revealed that\n                    <jats:italic>Leishmania<\/jats:italic>\n                    inhibits stimuli\u2010induced expression of a multiprotein signaling platform, NLRP3 inflammasome, which in turn inhibits caspase\u20101 activation mediated maturation of IL\u20101\u03b2 from its pro form. Attenuation of NLRP3 and pro\u2010IL\u20101\u03b2 in infection was found to result from decreased NF\u2010\u03baB activity. Transfecting infected cells with constitutively active NF\u2010\u03baB plasmid increased NLRP3 and pro\u2010IL\u20101\u03b2 expression but did not increase mature IL\u20101\u03b2, suggesting that IL\u20101\u03b2 maturation requires a second signal, which was found to be reactive oxygen species (ROS). Decreased NF\u2010\u03baB was attributed to increased expression of A20, a negative regulator of NF\u2010\u03baB signaling. Silencing A20 in infected cells restored NLRP3 and pro\u2010IL\u20101\u03b2 expression, but also increased matured IL\u20101\u03b2, implying an NF\u2010\u03baB\u2010independent A20\u2010modulated IL\u20101\u03b2 maturation. Macrophage ROS is primarily regulated by mitochondrial uncoupling protein 2 (UCP2), and UCP2\u2010silenced infected cells showed an increased IL\u20101\u03b2 level. Short hairpin RNA\u2010mediated knockdown of A20 and UCP2 in infected mice independently documented decreased liver and spleen parasite burden and increased IL\u20101\u03b2 production. These results suggest that\n                    <jats:italic>Leishmania<\/jats:italic>\n                    exploits A20 and UCP2 to impair inflammasome activation for disease propagation.\u2014Gupta, A. K., Ghosh, K., Palit, S., Barua, J., Das, P. K., Ukil, A.\n                    <jats:italic>Leishmania donovani<\/jats:italic>\n                    inhibits inflammasome\u2010dependent macrophage activation by exploiting the negative regulatory proteins A20 and UCP2. FASEB J. 31, 5087\u20135101 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700407r","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T20:40:26Z","timestamp":1501620026000},"page":"5087-5101","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["<i>Leishmania donovani<\/i>\n                    inhibits inflammasome\u2010dependent macrophage activation by exploiting the negative regulatory proteins A20 and UCP2"],"prefix":"10.1096","volume":"31","author":[{"given":"Anand Kumar","family":"Gupta","sequence":"first","affiliation":[{"name":"Infectious Diseases and Immunology Division Council of Scientific and Industrial Resarch (CSIR)\u2010Indian Institute of Chemical Biology Kolkata 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