{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:24:11Z","timestamp":1787498651709,"version":"build-2736575974"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>While there is evidence that Ebola virus (EBOV) antagonizes the antiviral type I interferon (IFN-I) response, the role of IFN-I for EBOV disease remains controversial, as initially protective responses may contribute to disease pathogenesis later.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed patient data from the 2014\u20132016 West Africa epidemic with a combination of machine learning and mathematical modeling to identify predictive immune mediators and reconstruct their temporal dynamics in survivors and non-survivors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results suggest that IFN-I response in survivors occurs before symptom onset, while non-survivors mount IFN-I responses 3\u20134 days later, although with a similar strength. This delayed IFN-I response overlaps in time with IL-12 signals in non-survivors. As optimal T cell activation requires a particular temporal sequence in cytokine signals, this impairs the development of T cell-based cellular immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The presented patient data analysis helps reconcile the seemingly contradictory role of IFN-I in EBOV disease from a cytokine dynamics perspective and supports the theory of sequential T cell activation, according to which a dysregulated temporal sequence of cytokine signals keeps T cells unresponsive to the pathogen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1806697","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:36:20Z","timestamp":1776922580000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Delayed type I interferon response and the subsequent out-of-sequence cytokine signal inhibit T cell induction in non-surviving Ebola virus-infected patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Gang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research","place":["Braunschweig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi\u0161a","family":"Korva","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana","place":["Ljubljana, Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Mu\u00f1oz-Fontela","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy","family":"Kerber","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian C.","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research","place":["Braunschweig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Meyer-Hermann","sequence":"additional","affiliation":[{"name":"Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz 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