{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:56:32Z","timestamp":1789955792557,"version":"4.0.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":2432,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>IFN-stimulated gene (ISG) 15 is a ubiquitin-like protein induced after type I IFN stimulation. There is a dearth of in vivo models to study free unconjugated ISG15 function. We found that free ISG15 enhances the production of IFN-\u03b3 and IL-1\u03b2 during murine infection with Toxoplasma gondii. In our model, ISG15 is induced in a type I IFN\u2013dependent fashion and released into the serum. Increased ISG15 levels are dependent on an actively invading and replicating parasite. Two cysteine residues in the hinge domain are necessary determinants for ISG15 to induce increased cytokine levels during infection. Increased ISG15 is concurrent with an influx of IL-1\u03b2\u2013producing CD8\u03b1+ dendritic cells to the site of infection. In this article, we present Toxoplasma infection as a novel in vivo murine model to study the immunomodulatory properties of free ISG15 and uniquely link it to IL-1\u03b2 production by CD8\u03b1+ dendritic cells driven by two cysteines in the hinge region of the protein.<\/jats:p>","DOI":"10.4049\/jimmunol.1701322","type":"journal-article","created":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T11:35:15Z","timestamp":1528716915000},"page":"604-614","source":"Crossref","is-referenced-by-count":44,"title":["Cysteine-Reactive Free ISG15 Generates IL-1\u03b2\u2013Producing CD8\u03b1+ Dendritic Cells at the Site of Infection"],"prefix":"10.1093","volume":"201","author":[{"given":"Anna","family":"Napolitano","sequence":"first","affiliation":[{"name":"Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute , London NW1 1AT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarthe G","family":"van der Veen","sequence":"additional","affiliation":[{"name":"Immunobiology Laboratory, The Francis Crick Institute , London NW1 1AT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Bunyan","sequence":"additional","affiliation":[{"name":"Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute , London NW1 1AT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-7226","authenticated-orcid":false,"given":"Annabel","family":"Borg","sequence":"additional","affiliation":[{"name":"Structural Biology, The Francis Crick Institute , London NW1 1AT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Frith","sequence":"additional","affiliation":[{"name":"Protein Analysis and Proteomics Laboratory, The Francis Crick Institute , London NW1 1AT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Howell","sequence":"additional","affiliation":[{"name":"Protein Analysis and Proteomics Laboratory, The Francis Crick Institute , London NW1 1AT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svend","family":"Kjaer","sequence":"additional","affiliation":[{"name":"Structural Biology, The Francis Crick Institute , London NW1 1AT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-5248","authenticated-orcid":false,"given":"Antje","family":"Beling","sequence":"additional","affiliation":[{"name":"Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Institute of Biochemistry , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5416-8592","authenticated-orcid":false,"given":"Ambrosius P","family":"Snijders","sequence":"additional","affiliation":[{"name":"Protein Analysis and Proteomics Laboratory, The Francis Crick Institute , London NW1 1AT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1587-1944","authenticated-orcid":false,"given":"Klaus-Peter","family":"Knobeloch","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University of Freiburg , 79106 Freiburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva-Maria","family":"Frickel","sequence":"additional","affiliation":[{"name":"Host-Toxoplasma Interaction Laboratory, The Francis Crick Institute , London NW1 1AT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,7,15]]},"reference":[{"key":"2025030417570283800_r1","doi-asserted-by":"crossref","first-page":"7806","DOI":"10.1016\/S0021-9258(18)42585-9","article-title":"The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular proteins","volume":"267","author":"Loeb","year":"1992","journal-title":"J. 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