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In the current study, we found that, whereas primary human monocytes produced interleukin-1beta (IL-1\u03b2) in response to<jats:italic>T.\u00a0gondii<\/jats:italic>infection, human neutrophils from the same blood donors did not. Moreover,<jats:italic>T.\u00a0gondii<\/jats:italic>inhibited lipopolysaccharide (LPS)-induced IL-1\u03b2 synthesis in human peripheral blood neutrophils. IL-1\u03b2 suppression required active parasite invasion, since heat-killed or mycalolide B-treated parasites did not inhibit IL-1\u03b2 release. By investigating the mechanisms involved in this process, we found that<jats:italic>T.\u00a0gondii<\/jats:italic>infection of neutrophils treated with LPS resulted in reduced transcript levels of<jats:italic>IL-1\u03b2<\/jats:italic>and<jats:italic>NLRP3<\/jats:italic>and reduced protein levels of pro-IL-1\u03b2, mature IL-1\u03b2, and the inflammasome sensor NLRP3. In<jats:italic>T.\u00a0gondii<\/jats:italic>-infected neutrophils stimulated with LPS, the levels of MyD88, TRAF6, IKK\u03b1, IKK\u03b2, and phosphorylated IKK\u03b1\/\u03b2 were not affected. However, LPS-induced I\u03baB\u03b1 degradation and p65 phosphorylation were reduced in<jats:italic>T.\u00a0gondii-<\/jats:italic>infected neutrophils, and degradation of I\u03baB\u03b1 was reversed by treatment with the proteasome inhibitor MG-132. Finally, we observed that<jats:italic>T.\u00a0gondii<\/jats:italic>inhibited the cleavage and activity of caspase-1 in human neutrophils. These results indicate that<jats:italic>T.\u00a0gondii<\/jats:italic>suppression of IL-1\u03b2 involves a two-pronged strategy whereby<jats:italic>T.\u00a0gondii<\/jats:italic>inhibits both NF-\u03baB signaling and activation of the NLRP3 inflammasome. These findings represent a novel mechanism of<jats:italic>T.\u00a0gondii<\/jats:italic>evasion of human neutrophil-mediated host defense by targeting the production of IL-1\u03b2.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold><jats:italic>Toxoplasma gondii<\/jats:italic>is an obligate intracellular parasite that infects approximately one-third of humans worldwide and can invade virtually any nucleated cell in the human body. Although it is well documented that neutrophils infiltrate the site of acute<jats:italic>T.\u00a0gondii<\/jats:italic>infection, there is limited understanding of how human neutrophils respond to<jats:italic>T.\u00a0gondii<\/jats:italic>. Neutrophils control infectious pathogens by a variety of mechanisms, including the release of the cytokine IL-1\u03b2, a major driver of inflammation during infection. This study reveals that<jats:italic>T.\u00a0gondii<\/jats:italic>is able to inhibit IL-1\u03b2 production in human neutrophils by impairing the activation of the NF-\u03baB signaling pathway and by inhibiting the inflammasome, the protein complex responsible for IL-1\u03b2 maturation. This two-pronged strategy of targeting the IL-1\u03b2 pathway may facilitate the survival and spread of<jats:italic>T.\u00a0gondii<\/jats:italic>during acute infection.<\/jats:p>","DOI":"10.1128\/mbio.02027-17","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T13:00:37Z","timestamp":1518440437000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Evasion of Human Neutrophil-Mediated Host Defense during<i>Toxoplasma gondii<\/i>Infection"],"prefix":"10.1128","volume":"9","author":[{"given":"Tatiane S.","family":"Lima","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California, USA"},{"name":"Institute for Immunology, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanny","family":"Gov","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California, USA"},{"name":"Institute for Immunology, University of California, Irvine, Irvine, California, USA"}],"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, California, USA"},{"name":"Institute for Immunology, University of California, Irvine, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3024"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.11.011"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00471"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.2008.00345.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis508"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-52910-7.00028-3"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1556\/EuJMI.1.2011.1.3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.8.4515"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.8.4574"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.07.012"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.8.4822-4826.2000"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182000059242"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220272110"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"7369","DOI":"10.4049\/jimmunol.162.12.7369","article-title":"Human polymorphonuclear leukocytes produce IL-12, TNF-alpha, and the chemokines macrophage-inflammatory protein-1 alpha and -1 beta in response to Toxoplasma gondii antigens","volume":"162","author":"Bliss SK","year":"1999","unstructured":"Bliss SK, Marshall AJ, Zhang Y, Denkers EY. 1999. 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