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

Florian Wimmers; Michele Donato; Alex Kuo; Tal Ashuach; Shakti Gupta; Chunfeng Li; Mai Dvorak; Mariko Hinton Foecke; Sarah E. Chang; Thomas Hagan; Sanne E. De Jong; Holden T. Maecker; Robbert van der Most; Peggie Cheung; Mario Cortese; Steven E. Bosinger; Mark Davis; Nadine Rouphael; Shankar Subramaniam; Nir Yosef; Paul J. Utz; Purvesh Khatri; Bali Pulendran

doi:10.1016/j.cell.2021.05.039

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

Florian Wimmers, Michele Donato, Alex Kuo, Tal Ashuach, Shakti Gupta, Chunfeng Li, Mai Dvorak, Mariko Hinton Foecke, Sarah E. Chang, Thomas Hagan, Sanne E. De Jong, Holden T. Maecker, Robbert van der Most, Peggie Cheung, Mario Cortese, Steven E. Bosinger, Mark Davis, Nadine Rouphael, Shankar Subramaniam, Nir YosefPaul J. Utz, Purvesh Khatri, Bali Pulendran

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e21
Pages (from-to)	3915-3935
Number of pages	42
Journal	Cell
Volume	184
Issue number	15
Early online date	25 Jun 2021
DOIs	https://doi.org/10.1016/j.cell.2021.05.039
State	Published - 22 Jul 2021
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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Wimmers, F., Donato, M., Kuo, A., Ashuach, T., Gupta, S., Li, C., Dvorak, M., Foecke, M. H., Chang, S. E., Hagan, T., De Jong, S. E., Maecker, H. T., van der Most, R., Cheung, P., Cortese, M., Bosinger, S. E., Davis, M., Rouphael, N., Subramaniam, S., ... Pulendran, B. (2021). The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination. Cell, 184(15), 3915-3935. Article e21. https://doi.org/10.1016/j.cell.2021.05.039

@article{8a41953f19e647859fd37eb1fbcbbf97,

title = "The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination",

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{\textquoteright}s potential as an epigenetic adjuvant.",

author = "Florian Wimmers and Michele Donato and Alex Kuo and Tal Ashuach and Shakti Gupta and Chunfeng Li and Mai Dvorak and Foecke, \{Mariko Hinton\} and Chang, \{Sarah E.\} and Thomas Hagan and \{De Jong\}, \{Sanne E.\} and Maecker, \{Holden T.\} and \{van der Most\}, Robbert and Peggie Cheung and Mario Cortese and Bosinger, \{Steven E.\} and Mark Davis and Nadine Rouphael and Shankar Subramaniam and Nir Yosef and Utz, \{Paul J.\} and Purvesh Khatri and Bali Pulendran",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = jul,

day = "22",

doi = "10.1016/j.cell.2021.05.039",

language = "الإنجليزيّة",

volume = "184",

pages = "3915--3935",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "15",

}

Wimmers, F, Donato, M, Kuo, A, Ashuach, T, Gupta, S, Li, C, Dvorak, M, Foecke, MH, Chang, SE, Hagan, T, De Jong, SE, Maecker, HT, van der Most, R, Cheung, P, Cortese, M, Bosinger, SE, Davis, M, Rouphael, N, Subramaniam, S, Yosef, N, Utz, PJ, Khatri, P & Pulendran, B 2021, 'The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination', Cell, vol. 184, no. 15, e21, pp. 3915-3935. https://doi.org/10.1016/j.cell.2021.05.039

TY - JOUR

T1 - The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination

AU - Wimmers, Florian

AU - Donato, Michele

AU - Kuo, Alex

AU - Ashuach, Tal

AU - Gupta, Shakti

AU - Li, Chunfeng

AU - Dvorak, Mai

AU - Foecke, Mariko Hinton

AU - Chang, Sarah E.

AU - Hagan, Thomas

AU - De Jong, Sanne E.

AU - Maecker, Holden T.

AU - van der Most, Robbert

AU - Cheung, Peggie

AU - Cortese, Mario

AU - Bosinger, Steven E.

AU - Davis, Mark

AU - Rouphael, Nadine

AU - Subramaniam, Shankar

AU - Yosef, Nir

AU - Utz, Paul J.

AU - Khatri, Purvesh

AU - Pulendran, Bali

PY - 2021/7/22

Y1 - 2021/7/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85109852063&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2021.05.039

DO - 10.1016/j.cell.2021.05.039

M3 - مقالة

C2 - 34174187

SN - 0092-8674

VL - 184

SP - 3915

EP - 3935

JO - Cell

JF - Cell

IS - 15

M1 - e21

ER -

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

Abstract

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