{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:39:02Z","timestamp":1791304742948,"version":"4.3.1"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2014,2,18]],"date-time":"2014-02-18T00:00:00Z","timestamp":1392681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,2,28]],"date-time":"2014-02-28T00:00:00Z","timestamp":1393545600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2014,2,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Induction of immunity that limits<jats:named-content content-type=\"genus-species\">Toxoplasma gondii<\/jats:named-content>infection in mice is critically dependent on the activation of the innate immune response. In this study, we investigated the role of cytoplasmic nucleotide-binding domain and leucine-rich repeat containing a pyrin domain (NLRP) inflammasome sensors during acute toxoplasmosis in mice. We show that<jats:italic>in vitro Toxoplasma<\/jats:italic>infection of murine bone marrow-derived macrophages activates the NLRP3 inflammasome, resulting in the rapid production and cleavage of interleukin-1\u03b2 (IL-1\u03b2), with no measurable cleavage of IL-18 and no pyroptosis. Paradoxically,<jats:italic>Toxoplasma<\/jats:italic>-infected mice produced large quantities of IL-18 but had no measurable IL-1\u03b2 in their serum. Infection of mice deficient in NLRP3, caspase-1\/11, IL-1R, or the inflammasome adaptor protein ASC led to decreased levels of circulating IL-18, increased parasite replication, and death. Interestingly, mice deficient in NLRP1 also displayed increased parasite loads and acute mortality. Using mice deficient in IL-18 and IL-18R, we show that this cytokine plays an important role in limiting parasite replication to promote murine survival. Our findings reveal<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>as a novel activator of the NLRP1 and NLRP3 inflammasomes<jats:italic>in vivo<\/jats:italic>and establish a role for these sensors in host resistance to toxoplasmosis.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Inflammasomes are multiprotein complexes that are a major component of the innate immune system. They contain \u201csensor\u201d proteins that are responsible for detecting various microbial and environmental danger signals and function by activating caspase-1, an enzyme that mediates cleavage and release of the proinflammatory cytokines interleukin-1\u03b2 (IL-1\u03b2) and IL-18.<jats:named-content content-type=\"genus-species\">Toxoplasma gondii<\/jats:named-content>is a highly successful protozoan parasite capable of infecting a wide range of host species that have variable levels of resistance. We report here that<jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>is a novel activator of the NLRP1 and NLRP3 inflammasomes<jats:italic>in vivo<\/jats:italic>and establish a role for these sensors in host resistance to toxoplasmosis. Using mice deficient in IL-18 and IL-18R, we show that the IL-18 cytokine plays a pivotal role by limiting parasite replication to promote murine survival.<\/jats:p>","DOI":"10.1128\/mbio.01117-13","type":"journal-article","created":{"date-parts":[[2014,2,19]],"date-time":"2014-02-19T04:33:32Z","timestamp":1392784412000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":273,"title":["Dual Role for Inflammasome Sensors NLRP1 and NLRP3 in Murine Resistance to Toxoplasma gondii"],"prefix":"10.1128","volume":"5","author":[{"given":"Gezahegn","family":"Gorfu","sequence":"first","affiliation":[{"name":"Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly M.","family":"Cirelli","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariane B.","family":"Melo","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Mayer-Barber","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devorah","family":"Crown","sequence":"additional","affiliation":[{"name":"Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverly H.","family":"Koller","sequence":"additional","affiliation":[{"name":"Pulmonary Division, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA"},{"name":"Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Masters","sequence":"additional","affiliation":[{"name":"Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Sher","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Leppla","sequence":"additional","affiliation":[{"name":"Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahtab","family":"Moayeri","sequence":"additional","affiliation":[{"name":"Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen P. 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