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Upon cellular infection or stress, inflammasomes are activated, triggering maturation of proinflammatory cytokines and downstream cellular signaling mediated through the MyD88 adaptor.<jats:italic>Toxoplasma gondii<\/jats:italic>is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines that are important in innate immunity. In this study, susceptibility alleles for human congenital toxoplasmosis were identified in the NALP1 gene. To investigate the role of the NALP1 inflammasome during infection with<jats:italic>T. gondii<\/jats:italic>, we genetically engineered a human monocytic cell line for NALP1 gene knockdown by RNA interference. NALP1 silencing attenuated progression of<jats:italic>T. gondii<\/jats:italic>infection, with accelerated host cell death and eventual cell disintegration. In line with this observation, upregulation of the proinflammatory cytokines interleukin-1\u03b2 (IL-1\u03b2), IL-18, and IL-12 upon<jats:italic>T. gondii<\/jats:italic>infection was not observed in monocytic cells with NALP1 knockdown. These findings suggest that the NALP1 inflammasome is critical for mediating innate immune responses to<jats:italic>T. gondii<\/jats:italic>infection and pathogenesis. Although there have been recent advances in understanding the potent activity of inflammasomes in directing innate immune responses to disease, this is the first report, to our knowledge, on the crucial role of the NALP1 inflammasome in the pathogenesis of<jats:italic>T. gondii<\/jats:italic>infections in humans.<\/jats:p>","DOI":"10.1128\/iai.00898-10","type":"journal-article","created":{"date-parts":[[2010,11,23]],"date-time":"2010-11-23T04:07:46Z","timestamp":1290485266000},"page":"756-766","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":183,"title":["NALP1 Influences Susceptibility to Human Congenital Toxoplasmosis, Proinflammatory Cytokine Response, and Fate of<i>Toxoplasma gondii<\/i>-Infected Monocytic Cells"],"prefix":"10.1128","volume":"79","author":[{"given":"William H.","family":"Witola","sequence":"first","affiliation":[{"name":"Departments of Surgery (Ophthalmology) and Pediatrics (Infectious Disease), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Mui","sequence":"additional","affiliation":[{"name":"Departments of Surgery (Ophthalmology) and Pediatrics (Infectious Disease), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrey","family":"Hargrave","sequence":"additional","affiliation":[{"name":"Departments of Surgery (Ophthalmology) and Pediatrics (Infectious Disease), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Surgery (Ophthalmology) and Pediatrics (Infectious Disease), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Hypolite","sequence":"additional","affiliation":[{"name":"Laboratoire Adaptation et Pathoge\u0301nie des Micro-Organismes, CNRS UMR 5163, Universite\u0301 Joseph Fourier Grenoble 1, Institut Jean Roget, BP 170, 38042 Grenoble Cedex 9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Montpetit","sequence":"additional","affiliation":[{"name":"Centre d'Innovation, Ge\u0301nome Que\u0301bec, Montre\u0301al, Que\u0301bec H3A 1A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Cavailles","sequence":"additional","affiliation":[{"name":"Laboratoire Adaptation et Pathoge\u0301nie des Micro-Organismes, CNRS UMR 5163, Universite\u0301 Joseph Fourier Grenoble 1, Institut Jean Roget, BP 170, 38042 Grenoble Cedex 9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordelia","family":"Bisanz","sequence":"additional","affiliation":[{"name":"Laboratoire Adaptation et Pathoge\u0301nie des Micro-Organismes, CNRS UMR 5163, Universite\u0301 Joseph Fourier Grenoble 1, Institut Jean Roget, BP 170, 38042 Grenoble Cedex 9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-France","family":"Cesbron-Delauw","sequence":"additional","affiliation":[{"name":"Laboratoire Adaptation et Pathoge\u0301nie des Micro-Organismes, CNRS UMR 5163, Universite\u0301 Joseph Fourier Grenoble 1, Institut Jean Roget, BP 170, 38042 Grenoble Cedex 9, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert J.","family":"Fournie\u0301","sequence":"additional","affiliation":[{"name":"INSERM, U563, F-31000 Toulouse, France"},{"name":"University Toulouse III Paul Sabatier, F-31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"McLeod","sequence":"additional","affiliation":[{"name":"Departments of Surgery (Ophthalmology) and Pediatrics (Infectious Disease), The University of Chicago, Chicago, Illinois 60637"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1547"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.139.5.1154"},{"key":"e_1_3_3_4_2","first-page":"15","volume":"4","year":"1996","unstructured":"Berridge, M. 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