Interferon-induced activation of dendritic cells and monocytes by yellow fever vaccination correlates with early antibody responses
Yellow fever vaccination provides long-lasting protection and is a unique model for studying the immune response to an acute RNA virus infection in humans. To elucidate the early innate immune events preceding the rapid generation of protective immunity, we performed transcriptome analysis of human blood dendritic cell (DC) and monocyte subpopulations before and 3, 7, 14, and 28 d after vaccination. We detected temporary upregulation of IFN-stimulated genes (ISG) in all DC and monocyte subsets on days 3 and 7 after vaccination as well as cell type-specific responses and response kinetics. Single-cell RNA sequencing revealed rapid appearance of activated DC and monocyte clusters dominated by ISGs, inflammatory chemokines, and genes involved in antigen processing and presentation. This was confirmed by flow cytometric analysis in a large cohort of vaccinees. We identified SIGLEC1/CD169 upregulation as a sensitive indicator of the transient IFN-induced activation state elicited in DCs and monocytes by YF17D vaccination correlating with early protective IgM antibody responses.
Authors
- Lisa Lehmann (ORCID: https://orcid.org/0000-0002-5153-3371)
- Antonio Santos‐Peral (ORCID: https://orcid.org/0000-0002-2167-5432)
- Simon Rothenfußer (ORCID: https://orcid.org/0000-0003-1151-7614)
- Anne Krug (ORCID: https://orcid.org/0000-0002-9556-7207)
- Elena Winheim (ORCID: https://orcid.org/0000-0002-0364-662X)
- Magdalena Zaucha (ORCID: https://orcid.org/0000-0002-3590-1525)
- Tobias Straub (ORCID: https://orcid.org/0000-0002-0547-0453)
- Katharina Eisenächer
- Giovanna Barba–Spaeth (ORCID: https://orcid.org/0000-0003-2069-9501)
- Linus Rinke (ORCID: https://orcid.org/0000-0002-7563-7116)
- Michael Pritsch (ORCID: https://orcid.org/0000-0001-7383-8750)
- Sebastian Goresch (ORCID: https://orcid.org/0009-0006-3586-6498)
- Tamara Ehm
- Sandra Riemer
Institutions
- Centre National de la Recherche Scientifique (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Center for Environmental Health (US)
- Helmholtz Zentrum München (DE)
- Institute of Immunology (HR)
- Hospital for Tropical Diseases (VN)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-05-07
- DOI
- https://doi.org/10.1073/pnas.2422236122
- Citations
- 3
- Primary Topic
- Immune responses and vaccinations
- Type
- article
- Field-Weighted Citation Impact
- 2.39
Funders
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Evangelisches Studienwerk Villigst
- Friedrich-Baur-Stiftung
- HORIZON EUROPE Framework Programme
- Helmholtz Zentrum München