20.500.12556/RUL-183189 Delayed type I interferon response and the subsequent out-of-sequence cytokine signal inhibit T cell induction in non-surviving Ebola virus-infected patients Introduction: 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. Methods: We analyzed patient data from the 2014-2016 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. Results: Our results suggest that IFN-I response in survivors occurs before symptom onset, while non-survivors mount IFN-I responses 3-4 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. Discussion: 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. Ebola virus cytokine dynamics innate adaptive immune crosstalk machine learning - ML mathematical model sequential cytokine signaling type I interferon virus Ebola dinamika citokinov interakcija med prirojenim in pridobljenim imunskim odzivom strojno učenje - ML matematični model sekvenčno signaliziranje citokinov interferon tipa I true false true Angleški jezik Slovenski jezik Članek v reviji 2026-06-07 06:14:43 2026-06-07 06:14:53 2026-07-17 10:50:09 0000-00-00 00:00:00 2026 0 0 10 str. art. 1806697 Vol. 17 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-097 1664-3224 10.3389/fimmu.2026.1806697 280576771 RAZ_Zhao_Gang_2026.pdf RAZ_Zhao_Gang_2026.pdf 1 65D8B0EAC5F757183E4114713E85F180 658dbd2a232d051ad5d44de8db407696fb6ef5e4c4b65bc8e7d845497b9546e5 9e8d9c4e-6228-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=235057 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1806697/full 1 102ae0e9-6227-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=235056 Medicinska fakulteta 0 0 0