{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:42:11Z","timestamp":1792460531360,"version":"4.5.0"},"reference-count":39,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"108","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2025,6,20]]},"abstract":"<jats:p>\n                    Efferocytosis, wherein phagocytes engulf dead or dying cells, is a critical function of macrophages that supports cellular turnover, tissue repair, and resolution of inflammation. Despite its well-established anti-inflammatory mechanism in homeostasis, whether efferocytosis remains immunologically silent in the context of dysregulated immune responses such as sepsis or systemic inflammatory response syndrome (SIRS) has not been investigated. Here, we used mouse models of tumor necrosis factor (TNF)\u2013induced SIRS and\n                    <jats:italic toggle=\"yes\">Escherichia coli\u2013<\/jats:italic>\n                    induced septic peritonitis to uncover a potential negative consequence of efferocytosis. We found that when activated with TNF, phagocytes efferocytosing neutrophils initiated a caspase-8\u2013dependent, but NLRP3 inflammasome\u2013independent, form of pyroptosis, which we termed \u201cefferoptosis.\u201d The maturation of IL-1\u03b2, a hallmark of pyroptotic cell death, also occurred independently of canonical inflammasome activation, supporting direct cleavage by caspase-8. Inhibition of efferocytosis protected mice against TNF-induced SIRS, suggesting that efferoptosis contributes to the pathology of sepsis and other TNF-mediated inflammatory conditions.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.adq0043","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T13:58:17Z","timestamp":1750427897000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":26,"title":["TNF switches homeostatic efferocytosis to lytic caspase-8\u2013dependent pyroptosis and IL-1\u03b2 maturation"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3006-5780","authenticated-orcid":true,"given":"Hayley I.","family":"Muendlein","sequence":"first","affiliation":[{"name":"Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson M.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9215-3351","authenticated-orcid":true,"given":"Jamie","family":"Leiriao","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8109-7339","authenticated-orcid":true,"given":"Mei-An","family":"Nolan","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Judge","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9580-6993","authenticated-orcid":true,"given":"Irina","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Batorsky","sequence":"additional","affiliation":[{"name":"Tufts Institute for Artificial Intelligence (TIAI), Tufts University, Medford, MA 02155, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5375-6587","authenticated-orcid":true,"given":"Alexander","family":"Poltorak","sequence":"additional","affiliation":[{"name":"Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA."},{"name":"Graduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1252809"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801394105"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20210425"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01394-13"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401168"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094359"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546262"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0710-y"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2018.03.058"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-019-0911-7"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-06-1887"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.101.6.1481"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.152.10.5041"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/cc10059"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.add0665"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1809548115"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau2818"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019101638"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3878"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401711"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","unstructured":"Y.-X. 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