Cargando…
Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination
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...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093110/ https://www.ncbi.nlm.nih.gov/pubmed/32204792 http://dx.doi.org/10.7554/eLife.52473 |
_version_ | 1783510232952995840 |
---|---|
author | Stebegg, Marisa Bignon, Alexandre Hill, Danika Lea Silva-Cayetano, Alyssa Krueger, Christel Vanderleyden, Ine Innocentin, Silvia Boon, Louis Wang, Jiong Zand, Martin S Dooley, James Clark, Jonathan Liston, Adrian Carr, Edward Linterman, Michelle A |
author_facet | Stebegg, Marisa Bignon, Alexandre Hill, Danika Lea Silva-Cayetano, Alyssa Krueger, Christel Vanderleyden, Ine Innocentin, Silvia Boon, Louis Wang, Jiong Zand, Martin S Dooley, James Clark, Jonathan Liston, Adrian Carr, Edward Linterman, Michelle A |
author_sort | Stebegg, Marisa |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7093110 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-70931102020-03-25 Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination Stebegg, Marisa Bignon, Alexandre Hill, Danika Lea Silva-Cayetano, Alyssa Krueger, Christel Vanderleyden, Ine Innocentin, Silvia Boon, Louis Wang, Jiong Zand, Martin S Dooley, James Clark, Jonathan Liston, Adrian Carr, Edward Linterman, Michelle A eLife Immunology and Inflammation 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. eLife Sciences Publications, Ltd 2020-03-24 /pmc/articles/PMC7093110/ /pubmed/32204792 http://dx.doi.org/10.7554/eLife.52473 Text en © 2020, Stebegg et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Stebegg, Marisa Bignon, Alexandre Hill, Danika Lea Silva-Cayetano, Alyssa Krueger, Christel Vanderleyden, Ine Innocentin, Silvia Boon, Louis Wang, Jiong Zand, Martin S Dooley, James Clark, Jonathan Liston, Adrian Carr, Edward Linterman, Michelle A Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination |
title | Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination |
title_full | Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination |
title_fullStr | Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination |
title_full_unstemmed | Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination |
title_short | Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination |
title_sort | rejuvenating conventional dendritic cells and t follicular helper cell formation after vaccination |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093110/ https://www.ncbi.nlm.nih.gov/pubmed/32204792 http://dx.doi.org/10.7554/eLife.52473 |
work_keys_str_mv | AT stebeggmarisa rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT bignonalexandre rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT hilldanikalea rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT silvacayetanoalyssa rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT kruegerchristel rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT vanderleydenine rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT innocentinsilvia rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT boonlouis rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT wangjiong rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT zandmartins rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT dooleyjames rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT clarkjonathan rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT listonadrian rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT carredward rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination AT lintermanmichellea rejuvenatingconventionaldendriticcellsandtfollicularhelpercellformationaftervaccination |