The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination,Cell

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The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination
Cell ( IF 64.5 ) Pub Date : 2021-06-25 , DOI: 10.1016/j.cell.2021.05.039
Florian Wimmers ₁ , Michele Donato ₂ , Alex Kuo ₃ , Tal Ashuach ₄ , Shakti Gupta ₅ , Chunfeng Li ₁ , Mai Dvorak ₃ , Mariko Hinton Foecke ₃ , Sarah E Chang ₃ , Thomas Hagan ₁ , Sanne E De Jong ₁ , Holden T Maecker ₁ , Robbert van der Most ₆ , Peggie Cheung ₇ , Mario Cortese ₁ , Steven E Bosinger ₈ , Mark Davis ₉ , Nadine Rouphael ₁₀ , Shankar Subramaniam ₅ , Nir Yosef ₁₁ , Paul J Utz ₃ , Purvesh Khatri ₂ , Bali Pulendran ₁₂

Affiliation

Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA 94305, USA.
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Electrical Engineering and Computer Sciences and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive MC 0412, La Jolla, CA 92093, USA.
GSK, 1330 Rixensart, Belgium.
Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
Department of Electrical Engineering and Computer Sciences and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Chan-Zuckerberg Biohub, San Francisco, CA, USA.
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Emerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza induced persistently diminished H3K27ac in monocytes and myeloid dendritic cells (mDCs), which was associated with impaired cytokine responses to Toll-like receptor stimulation. Single-cell ATAC-seq analysis revealed an epigenomically distinct subcluster of monocytes with reduced chromatin accessibility at AP-1-targeted loci after vaccination. Similar effects were observed in response to vaccination with the AS03-adjuvanted H5N1 pandemic influenza vaccine. However, this vaccine also stimulated persistently increased chromatin accessibility at interferon response factor (IRF) loci in monocytes and mDCs. This was associated with elevated expression of antiviral genes and heightened resistance to the unrelated Zika and Dengue viruses. These results demonstrate that vaccination stimulates persistent epigenomic remodeling of the innate immune system and reveal AS03’s potential as an epigenetic adjuvant.

中文翻译：

流感疫苗免疫的单细胞表观基因组和转录景观

新的证据表明表观基因组在免疫中发挥着重要作用。在这里，我们在单细胞水平上绘制了人类流感疫苗免疫的表观基因组和转录图谱。季节性流感疫苗接种可导致单核细胞和髓样树突状细胞 (mDC) 中的 H3K27ac 持续减少，这与 Toll 样受体刺激的细胞因子反应受损有关。单细胞 ATAC-seq 分析揭示了表观基因组独特的单核细胞亚群，在接种疫苗后，AP-1 靶向位点的染色质可及性降低。在接种含有 AS03 佐剂的 H5N1 大流行性流感疫苗后也观察到了类似的效果。然而，这种疫苗还刺激单核细胞和 mDC 中干扰素反应因子 (IRF) 位点的染色质可及性持续增加。这与抗病毒基因表达升高以及对不相关的寨卡病毒和登革热病毒的抵抗力增强有关。这些结果表明，疫苗接种可刺激先天免疫系统的持续表观基因组重塑，并揭示 AS03 作为表观遗传佐剂的潜力。

更新日期：2021-07-22

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