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We found that the intracellular protozoan parasite Toxoplasma gondii induced an early IL-1\u03b2 response (within 4 h) in primary human peripheral blood monocytes isolated from healthy donors. This process involved upregulation of IL-1\u03b2, IL-1RN (IL-1R antagonist), and NLRP3 transcripts, de novo protein synthesis, and the release of pro- and mature IL-1\u03b2 from infected primary monocytes. The released pro\u2013IL-1\u03b2 was cleavable to mature bioactive IL-1\u03b2 in the extracellular space by the protease caspase-1. Treatment of primary monocytes with the NLRP3 inhibitor MCC950 or with extracellular potassium significantly reduced IL-1\u03b2 cleavage and release in response to T. gondii infection, without affecting the release of TNF-\u03b1, and indicated a role for the inflammasome sensor NLRP3 and for potassium efflux in T. gondii\u2013induced IL-1\u03b2 production. Interestingly, T. gondii infection did not induce an IL-1\u03b2 response in primary human macrophages derived from the same blood donors as the monocytes. Consistent with this finding, NLRP3 was downregulated during the differentiation of monocytes to macrophages and was not induced in macrophages during T. gondii infection. To our knowledge, these findings are the first to identify NLRP3 as an inflammasome sensor for T. gondii in primary human peripheral blood cells and to define an upstream regulator of its activation through the release of intracellular potassium.<\/jats:p>","DOI":"10.4049\/jimmunol.1700245","type":"journal-article","created":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T01:05:59Z","timestamp":1505351159000},"page":"2855-2864","source":"Crossref","is-referenced-by-count":84,"title":["NLRP3 and Potassium Efflux Drive Rapid IL-1\u03b2 Release from Primary Human Monocytes during <i>Toxoplasma gondii<\/i> Infection"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9441-3628","authenticated-orcid":false,"given":"Lanny","family":"Gov","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California , Irvine, Irvine, CA 92697; and , Irvine, Irvine, CA 92697"},{"name":"Institute for Immunology, University of California , Irvine, Irvine, CA 92697; and , Irvine, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California , Irvine, Irvine, CA 92697; and , Irvine, Irvine, CA 92697"},{"name":"Institute for Immunology, University of California , Irvine, Irvine, CA 92697; and , Irvine, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiane S","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California , Irvine, Irvine, CA 92697; and , Irvine, Irvine, CA 92697"},{"name":"Institute for Immunology, University of California , Irvine, Irvine, CA 92697; and , Irvine, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Pandori","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California , Irvine, Irvine, CA 92697; and , Irvine, Irvine, CA 92697"},{"name":"Institute for Immunology, University of California , Irvine, Irvine, CA 92697; and , Irvine, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa B","family":"Lodoen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California , Irvine, Irvine, CA 92697; and , Irvine, Irvine, CA 92697"},{"name":"Institute for Immunology, University of California , Irvine, Irvine, CA 92697; and , Irvine, Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,10,15]]},"reference":[{"key":"2025030614475487000_r1","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","article-title":"Toxoplasmosis","volume":"363","author":"Montoya","year":"2004","journal-title":"Lancet"},{"key":"2025030614475487000_r2","first-page":"33","article-title":"Role of TNF and IL-1 in infections with Toxoplasma gondii","volume":"69","author":"Chang","year":"1990","journal-title":"Immunology"},{"key":"2025030614475487000_r3","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.4049\/jimmunol.155.9.4347","article-title":"IL-1 beta is required for IL-12 to induce production of IFN-gamma by NK cells. 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