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黄热病疫苗接种诱导的树突状细胞和单核细胞激活与早期抗体反应相关。

Interferon-induced activation of dendritic cells and monocytes by yellow fever vaccination correlates with early antibody responses.

作者信息

Winheim Elena, Santos-Peral Antonio, Ehm Tamara, Rinke Linus, Riemer Sandra, Zaucha Magdalena, Goresch Sebastian, Lehmann Lisa, Eisenächer Katharina, Pritsch Michael, Barba-Spaeth Giovanna, Straub Tobias, Rothenfusser Simon, Krug Anne B

机构信息

Institute for Immunology, Biomedical Center, Faculty of Medicine, LMU, Munich D-82152, Germany.

Division of Clinical Pharmacology, University Hospital, Ludwig-Maximilans-Universität München, Munich D-80336, Germany.

出版信息

Proc Natl Acad Sci U S A. 2025 May 13;122(19):e2422236122. doi: 10.1073/pnas.2422236122. Epub 2025 May 7.

DOI:10.1073/pnas.2422236122
PMID:40333758
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12088451/
Abstract

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.

摘要

黄热病疫苗接种可提供持久的保护，是研究人类对急性RNA病毒感染的免疫反应的独特模型。为了阐明在快速产生保护性免疫之前的早期先天性免疫事件，我们对接种疫苗前以及接种后3、7、14和28天的人血树突状细胞（DC）和单核细胞亚群进行了转录组分析。我们在接种疫苗后第3天和第7天检测到所有DC和单核细胞亚群中IFN刺激基因（ISG）的暂时上调，以及细胞类型特异性反应和反应动力学。单细胞RNA测序揭示了由ISG、炎性趋化因子以及参与抗原加工和呈递的基因主导的活化DC和单核细胞簇的快速出现。这在一大群疫苗接种者中通过流式细胞术分析得到了证实。我们确定SIGLEC1/CD169上调是YF17D疫苗接种在DC和单核细胞中引发的短暂IFN诱导活化状态的敏感指标，与早期保护性IgM抗体反应相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/00cd799afdb6/pnas.2422236122fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/84487bbbece4/pnas.2422236122fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/1281c730e193/pnas.2422236122fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/86a18850edff/pnas.2422236122fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/63369798c710/pnas.2422236122fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/44c3f2afb759/pnas.2422236122fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/a2c3296db386/pnas.2422236122fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/00cd799afdb6/pnas.2422236122fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/84487bbbece4/pnas.2422236122fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/1281c730e193/pnas.2422236122fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/86a18850edff/pnas.2422236122fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/63369798c710/pnas.2422236122fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/44c3f2afb759/pnas.2422236122fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/a2c3296db386/pnas.2422236122fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37f2/12088451/00cd799afdb6/pnas.2422236122fig07.jpg

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本文引用的文献

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Cell Rep Med. 2025 Feb 18;6(2):101946. doi: 10.1016/j.xcrm.2025.101946. Epub 2025 Feb 11.
2
Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection.既往黄病毒感染使黄热病疫苗对交叉反应性抗体的反应产生偏倚，从而有可能增强登革病毒感染。
Nat Commun. 2024 Feb 24;15(1):1696. doi: 10.1038/s41467-024-45806-x.
3
Global and cell type-specific immunological hallmarks of severe dengue progression identified via a systems immunology approach.
通过系统免疫学方法鉴定的严重登革热进展的全球和细胞类型特异性免疫特征。
Nat Immunol. 2023 Dec;24(12):2150-2163. doi: 10.1038/s41590-023-01654-3. Epub 2023 Oct 23.
4
Transitional dendritic cells are distinct from conventional DC2 precursors and mediate proinflammatory antiviral responses.过渡性树突状细胞有别于传统的 DC2 前体细胞，并介导促炎性抗病毒反应。
Nat Immunol. 2023 Aug;24(8):1265-1280. doi: 10.1038/s41590-023-01545-7. Epub 2023 Jul 6.
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CD4 T cell calibration of antigen-presenting cells optimizes antiviral CD8 T cell immunity.CD4 T 细胞对抗原提呈细胞的校准优化了抗病毒 CD8 T 细胞免疫。
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