tetano
Editor, Senior Moderator
Cell
. 2021 Jun 22;S0092-8674(21)00692-9.
doi: 10.1016/j.cell.2021.05.039. Online ahead of print.
The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination
Florian Wimmers[SUP] 1 [/SUP], Michele Donato[SUP] 2 [/SUP], Alex Kuo[SUP] 3 [/SUP], Tal Ashuach[SUP] 4 [/SUP], Shakti Gupta[SUP] 5 [/SUP], Chunfeng Li[SUP] 1 [/SUP], Mai Dvorak[SUP] 3 [/SUP], Mariko Hinton Foecke[SUP] 3 [/SUP], Sarah E Chang[SUP] 3 [/SUP], Thomas Hagan[SUP] 1 [/SUP], Sanne E De Jong[SUP] 1 [/SUP], Holden T Maecker[SUP] 1 [/SUP], Robbert van der Most[SUP] 6 [/SUP], Peggie Cheung[SUP] 7 [/SUP], Mario Cortese[SUP] 1 [/SUP], Steven E Bosinger[SUP] 8 [/SUP], Mark Davis[SUP] 9 [/SUP], Nadine Rouphael[SUP] 10 [/SUP], Shankar Subramaniam[SUP] 5 [/SUP], Nir Yosef[SUP] 11 [/SUP], Paul J Utz[SUP] 3 [/SUP], Purvesh Khatri[SUP] 2 [/SUP], Bali Pulendran[SUP] 12 [/SUP]
Affiliations
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.
Keywords: adjuvant; antiviral immunity; epigenome; influenza; innate memory; monocyte; single cell; systems biology; trained immunity; vaccines.
. 2021 Jun 22;S0092-8674(21)00692-9.
doi: 10.1016/j.cell.2021.05.039. Online ahead of print.
The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination
Florian Wimmers[SUP] 1 [/SUP], Michele Donato[SUP] 2 [/SUP], Alex Kuo[SUP] 3 [/SUP], Tal Ashuach[SUP] 4 [/SUP], Shakti Gupta[SUP] 5 [/SUP], Chunfeng Li[SUP] 1 [/SUP], Mai Dvorak[SUP] 3 [/SUP], Mariko Hinton Foecke[SUP] 3 [/SUP], Sarah E Chang[SUP] 3 [/SUP], Thomas Hagan[SUP] 1 [/SUP], Sanne E De Jong[SUP] 1 [/SUP], Holden T Maecker[SUP] 1 [/SUP], Robbert van der Most[SUP] 6 [/SUP], Peggie Cheung[SUP] 7 [/SUP], Mario Cortese[SUP] 1 [/SUP], Steven E Bosinger[SUP] 8 [/SUP], Mark Davis[SUP] 9 [/SUP], Nadine Rouphael[SUP] 10 [/SUP], Shankar Subramaniam[SUP] 5 [/SUP], Nir Yosef[SUP] 11 [/SUP], Paul J Utz[SUP] 3 [/SUP], Purvesh Khatri[SUP] 2 [/SUP], Bali Pulendran[SUP] 12 [/SUP]
Affiliations
- PMID: 34174187
- DOI: 10.1016/j.cell.2021.05.039
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.
Keywords: adjuvant; antiviral immunity; epigenome; influenza; innate memory; monocyte; single cell; systems biology; trained immunity; vaccines.