{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:28:05Z","timestamp":1777354085744,"version":"3.51.4"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI121804"],"award-info":[{"award-number":["R01AI121804"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI155582"],"award-info":[{"award-number":["R01AI155582"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM113123"],"award-info":[{"award-number":["P20GM113123"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neutrophil extracellular traps (NETs) are implicated in host defense and inflammatory pathologies alike. A wide range of pathogen- and host-derived factors are known to induce NETs, yet the knowledge about specific receptor\u2013ligand interactions in this response is limited. We previously reported that macrophage-inducible C-type lectin (Mincle) regulates NET formation. In this article, we identify glycosphingolipid \u03b2-glucosylceramide (\u03b2-GlcCer) as a specific NET-inducing ligand of Mincle. We found that purified \u03b2-GlcCer induced NETs in mouse primary neutrophils in vitro and in vivo, and this effect was abrogated in Mincle deficiency. Cell-free \u03b2-GlcCer accumulated in the lungs of pneumonic mice, which correlated with pulmonary NET formation in wild-type, but not in Mincle\u2212\/\u2212, mice infected intranasally with Klebsiella pneumoniae. Although leukocyte infiltration by \u03b2-GlcCer administration in vivo did not require Mincle, NETs induced by this sphingolipid were important for bacterial clearance during Klebsiella infection. Mechanistically, \u03b2-GlcCer did not activate reactive oxygen species formation in neutrophils but required autophagy and glycolysis for NET formation, because ATG4 inhibitor NSC185058, as well as glycolysis inhibitor 2-deoxy-d-glucose, abrogated \u03b2-GlcCer\u2013induced NETs. Forced autophagy activation by tamoxifen could overcome the inhibitory effect of glycolysis blockage on \u03b2-GlcCer\u2013mediated NET formation, suggesting that autophagy activation is sufficient to induce NETs in response to this metabolite in the absence of glycolysis. Finally, \u03b2-GlcCer accumulated in the plasma of patients with systemic inflammatory response syndrome, and its levels correlated with the extent of systemic NET formation in these patients. Overall, our results posit \u03b2-GlcCer as a potent NET-inducing ligand of Mincle with diagnostic and therapeutic potential in inflammatory disease settings.<\/jats:p>","DOI":"10.4049\/jimmunol.2100855","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T16:08:22Z","timestamp":1657814902000},"page":"391-400","source":"Crossref","is-referenced-by-count":11,"title":["Glycolipid Metabolite \u03b2-Glucosylceramide Is a Neutrophil Extracellular Trap\u2013Inducing Ligand of Mincle Released during Bacterial Infection and Inflammation"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0189-1920","authenticated-orcid":false,"given":"Atul","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine & Health Sciences, The University of North Dakota , Grand Forks, ND"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3005-1311","authenticated-orcid":false,"given":"Arun","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine & Health Sciences, The University of North Dakota , Grand Forks, ND"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pooja","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine & Health Sciences, The University of North Dakota , Grand Forks, ND"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dustin L","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine & Health Sciences, The University of North Dakota , Grand Forks, ND"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3103-5786","authenticated-orcid":false,"given":"Randolph E","family":"Szlabick","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine & Health Sciences, The University of North Dakota , Grand Forks, ND"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5818-0276","authenticated-orcid":false,"given":"Mary O","family":"Aaland","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine & Health Sciences, The University of North Dakota , Grand Forks, ND"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibhuti B","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine & Health Sciences, The University of North Dakota , Grand Forks, ND"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyotika","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine & Health Sciences, The University of North Dakota , Grand Forks, ND"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"2025021008204133700_r1","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/JLB.3RU0620-375R","article-title":"The vitals of NETs","volume":"110","author":"Tan","year":"2021","journal-title":"J. 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