| Literature DB >> 34174187 |
Florian Wimmers1, Michele Donato2, Alex Kuo3, Tal Ashuach4, Shakti Gupta5, Chunfeng Li1, Mai Dvorak3, Mariko Hinton Foecke3, Sarah E Chang3, Thomas Hagan1, Sanne E De Jong1, Holden T Maecker1, Robbert van der Most6, Peggie Cheung7, Mario Cortese1, Steven E Bosinger8, Mark Davis9, Nadine Rouphael10, Shankar Subramaniam5, Nir Yosef11, Paul J Utz3, Purvesh Khatri2, Bali Pulendran12.
Abstract
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.Entities:
Keywords: adjuvant; antiviral immunity; epigenome; influenza; innate memory; monocyte; single cell; systems biology; trained immunity; vaccines
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Year: 2021 PMID： 34174187 PMCID： PMC8316438 DOI： 10.1016/j.cell.2021.05.039
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850