{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:27:04Z","timestamp":1780500424686,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012006","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01NS112516"],"award-info":[{"award-number":["R01NS112516"]}]},{"name":"National Institute of Health","award":["R21NS128551"],"award-info":[{"award-number":["R21NS128551"]}]},{"name":"National Institute of Health","award":["T32AI007496"],"award-info":[{"award-number":["T32AI007496"]}]},{"name":"National Institute of Health","award":["5T32GM136615"],"award-info":[{"award-number":["5T32GM136615"]}]},{"name":"National Institute of Health","award":["5T32NS1156573"],"award-info":[{"award-number":["5T32NS1156573"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10RR031633-01"],"award-info":[{"award-number":["S10RR031633-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018088","name":"School of Medicine, University of Virginia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018088","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Inflammasome activation is a robust innate immune mechanism that promotes inflammatory responses through the release of alarmins and leaderless cytokines, including IL-1\u03b1, IL-1\u03b2, and IL-18. Various stimuli, including infectious agents and cellular stress, cause inflammasomes to assemble and activate caspase-1. Then, caspase-1 cleaves targets that lead to pore formation and leaderless cytokine activation and release. <jats:italic>Toxoplasma gondii<\/jats:italic> has been shown to promote inflammasome formation, but the cell types utilizing caspase-1 and the downstream effects on immunological outcomes during acute <jats:italic>in vivo<\/jats:italic> infection have not been explored. Here, using knockout mice, we examine the role of caspase-1 responses during acute <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> infection globally and in <jats:italic>Cx3cr1<\/jats:italic>-positive populations. We provide <jats:italic>in vivo<\/jats:italic> evidence that caspase-1 expression is critical for, IL-18 release, optimal interferon-\u03b3 (IFN-\u03b3) production, monocyte and neutrophil recruitment to the site of infection, and parasite control. Specifically, we find that caspase-1 expression in <jats:italic>Cx3cr1<\/jats:italic>-positive cells drives IL-18 release, which potentiates CD4<jats:sup>+<\/jats:sup> T cell IFN-\u03b3 production and parasite control. Notably, our <jats:italic>Cx3cr1<\/jats:italic>-<jats:italic>Casp1<\/jats:italic> knockouts exhibited a selective T cell defect, mirroring the phenotype observed in <jats:italic>Il18<\/jats:italic> knockouts. In further support of this finding, treatment of <jats:italic>Cx3cr1<\/jats:italic>-<jats:italic>Casp1<\/jats:italic> knockout mice with recombinant IL-18 restored CD4<jats:sup>+<\/jats:sup> T cell IFN-\u03b3 responses and parasite control. Additionally, we show that neutrophil recruitment is dependent on IL-1 receptor accessory protein (IL-1RAP) signaling but is dispensable for parasite control. Overall, these experiments highlight the multifaceted role of caspase-1 in multiple cell populations contributing to specific pathways that collectively contribute to caspase-1 dependent immunity to <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012006","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T18:01:06Z","timestamp":1729792866000},"page":"e1012006","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Caspase-1 in Cx3cr1-expressing cells drives an IL-18-dependent T cell response that promotes parasite control during acute Toxoplasma gondii infection"],"prefix":"10.1371","volume":"20","author":[{"given":"Isaac W.","family":"Babcock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia A.","family":"Sibley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney A.","family":"Labuzan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen N.","family":"Cowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ish","family":"Sethi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seblework","family":"Alemu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail G.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Lukens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1355-2109","authenticated-orcid":true,"given":"Tajie H.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"issue":"6","key":"ppat.1012006.ref001","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern Recognition Receptors and Inflammation","volume":"140","author":"O Takeuchi","year":"2010","journal-title":"Cell"},{"issue":"4","key":"ppat.1012006.ref002","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.immuni.2007.10.002","article-title":"Intracellular NOD-like receptors in host defense and disease","volume":"27","author":"TD 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