Poster Presentation 18th International Symposium on Dendritic Cells 2026

RIG-I-like receptor-dependent type I Interferon regulates antigen dose and activation in yellow fever vaccine 17D-infected antigen presenting cells (#178)

Anne Krug 1 , Magdalena Zaucha 2 , Elena Winheim 1 , Antonio Santos-Peral 1 , Apurva Dhavale 1 , Margarita Shnipova 1 , Paul Schwarzlmueller 2 3 , Frank Dahlstroem 2 , Giulia Spielmann 2 , Magdalena K Scheck 2 , Linus Rinke 1 , Yiqi Huang 1 , Varvara Arzhakova 1 , Helen Stirling 2 , Katharina Eisenächer 1 , Hadi Karimzadeh 2 , Michael Pritsch 4 , Julia Spanier 5 , Ulrich Kalinke 5 , Amandine Bovay 6 , Daniel E Speiser 6 , Kilian Schober 7 8 , Ev-Marie Schuster 7 , Julia Thorn-Seshold 2 , Giovanna Barba-Spaeth 9 , Simon Rothenfusser 2
  1. Institute for Immunology, Biomedical Center (BMC), Faulty of Medicine, LMU Munich, Munich, Germany
  2. Division of Clinical Pharmacology, University Hospital, LMU Munich, Munich, Germany
  3. Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany
  4. Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, Munich, Germany
  5. TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover Medical School & Helmholtz Centre for Infection Research, Hannover, Germany
  6. Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
  7. Mikrobiologisches Institut-Klinische Mikrobiologies, Immunologie and Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
  8. FAU Profile Center Immunomedicine, FAU Erlangen-Nürnberg, Erlangen, Germany
  9. Institut Pasteur, Université de Paris, CNRS UMR 3569, Unité de Virologie Structurale, Paris, France

The live-attenuated yellow fever vaccine 17D-204 (YF17D) activates robust innate immune responses followed by rapid induction of adaptive immunity resulting in long-lasting protection. YF17D triggers the production of type I interferons (IFNs) which have a dual role in antigen presenting cells regulating their infection and contributing to their activation. Infection with YF17D was detected in primary human blood monocytes and conventional dendritic cells (DCs) and in monocyte-derived DCs but was highly restricted by type I IFN. Blocking IFNAR signaling in YF17D-infected DCs resulted in increased activation of YF17D-specific CD8+ T cells. Consistently, peak IFN-alpha plasma levels correlated inversely with the CD8+ T cells response in YF17D vaccinees. Loss of function experiments demonstrated a dominant role of retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and mitochondrial antiviral signaling protein (MAVS) for type I IFN induction and restriction of YF17D. The type I IFN response was mediated by 5’ tri- or diphosphate dsRNA intermediates that are formed during YF17D infection. In vivo proximity labelling (IPL) of RIG-I and next-generation sequencing confirmed interaction of RIG-I with YF17D-dsRNA in infected cells. Thus, YF17D-triggered RLR-signaling restricts viral infection through type I IFN and thus limits the production of viral antigens that can be presented to T cells.