Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination.
Adolescent
Adoptive Transfer
Adult
Aged
Aging
Animals
B-Lymphocytes
Bone Marrow Cells
CD11 Antigens
/ genetics
Chimera
Female
Germinal Center
/ physiology
Humans
Immunity, Humoral
Immunologic Memory
Influenza Vaccines
/ administration & dosage
Influenza, Human
/ prevention & control
Male
Mice
Mice, Knockout
Middle Aged
Orthomyxoviridae Infections
/ prevention & control
Receptor, Interferon alpha-beta
/ genetics
T Follicular Helper Cells
/ physiology
T-Lymphocytes, Helper-Inducer
/ physiology
Vaccination
Young Adult
ageing
dendritic cells
germinal centre response
human
immunology
inflammation
mouse
t follicular helper cells
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
24 03 2020
24 03 2020
Historique:
received:
05
10
2019
accepted:
12
03
2020
entrez:
25
3
2020
pubmed:
25
3
2020
medline:
10
4
2021
Statut:
epublish
Résumé
Germinal centres (GCs) are T follicular helper cell (Tfh)-dependent structures that form in response to vaccination, producing long-lived antibody secreting plasma cells and memory B cells that protect against subsequent infection. With advancing age the GC and Tfh cell response declines, resulting in impaired humoral immunity. We sought to discover what underpins the poor Tfh cell response in ageing and whether it is possible to correct it. Here, we demonstrate that older people and aged mice have impaired Tfh cell differentiation upon vaccination. This deficit is preceded by poor activation of conventional dendritic cells type 2 (cDC2) due to reduced type 1 interferon signalling. Importantly, the Tfh and cDC2 cell response can be boosted in aged mice by treatment with a TLR7 agonist. This demonstrates that age-associated defects in the cDC2 and Tfh cell response are not irreversible and can be enhanced to improve vaccine responses in older individuals.
Identifiants
pubmed: 32204792
doi: 10.7554/eLife.52473
pii: 52473
pmc: PMC7093110
doi:
pii:
Substances chimiques
CD11 Antigens
0
Ifnar1 protein, mouse
0
Influenza Vaccines
0
Itgax protein, mouse
0
Receptor, Interferon alpha-beta
156986-95-7
Banques de données
GEO
['GSE133148', 'GSE74813']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0407
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/B/000C0408
Pays : United Kingdom
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 675395
Organisme : H2020 European Research Council
ID : 637801
Informations de copyright
© 2020, Stebegg et al.
Déclaration de conflit d'intérêts
MS, AB, DH, AS, CK, IV, SI, LB, JW, MZ, JD, JC, AL, EC, ML No competing interests declared
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