Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination

Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination

To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age ≥65) adults receiving influenza vaccine in two consecutive seasons and identified those with strong or absent response to vaccine, including a subset...

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Main Authors: Thakar, Juilee, Mohanty, Subhasis, West, A. Phillip, Joshi, Samit R., Ueda, Ikuyo, Wilson, Jean, Meng, Hailong, Blevins, Tamara P., Tsang, Sui, Trentalange, Mark, Siconolfi, Barbara, Park, Koonam, Gill, Thomas M., Belshe, Robert B., Kaech, Susan M., Shadel, Gerald S., Kleinstein, Steven H., Shaw, Albert C.
Format: Online
Language:English
Published: Impact Journals LLC 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/
id pubmed-4356402
recordtype oai_dc
spelling pubmed-43564022015-03-20 Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination Thakar, Juilee Mohanty, Subhasis West, A. Phillip Joshi, Samit R. Ueda, Ikuyo Wilson, Jean Meng, Hailong Blevins, Tamara P. Tsang, Sui Trentalange, Mark Siconolfi, Barbara Park, Koonam Gill, Thomas M. Belshe, Robert B. Kaech, Susan M. Shadel, Gerald S. Kleinstein, Steven H. Shaw, Albert C. Research Paper To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age ≥65) adults receiving influenza vaccine in two consecutive seasons and identified those with strong or absent response to vaccine, including a subset of older adults meeting criteria for frailty. PBMCs obtained prior to vaccination (Day 0) and at day 2 or 4, day 7 and day 28 post-vaccine were subjected to gene expression microarray analysis. We defined a response signature and also detected induction of a type I interferon response at day 2 and a plasma cell signature at day 7 post-vaccine in young responders. The response signature was dysregulated in older adults, with the plasma cell signature induced at day 2, and was never induced in frail subjects (who were all non-responders). We also identified a mitochondrial signature in young vaccine responders containing genes mediating mitochondrial biogenesis and oxidative phosphorylation that was consistent in two different vaccine seasons and verified by analyses of mitochondrial content and protein expression. These results represent the first genome-wide transcriptional profiling analysis of age-associated dynamics following influenza vaccination, and implicate changes in mitochondrial biogenesis and function as a critical factor in human vaccine responsiveness. Impact Journals LLC 2015-01-14 /pmc/articles/PMC4356402/ /pubmed/25596819 Text en Copyright: © 2015 Thakar et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Thakar, Juilee
Mohanty, Subhasis
West, A. Phillip
Joshi, Samit R.
Ueda, Ikuyo
Wilson, Jean
Meng, Hailong
Blevins, Tamara P.
Tsang, Sui
Trentalange, Mark
Siconolfi, Barbara
Park, Koonam
Gill, Thomas M.
Belshe, Robert B.
Kaech, Susan M.
Shadel, Gerald S.
Kleinstein, Steven H.
Shaw, Albert C.
spellingShingle Thakar, Juilee
Mohanty, Subhasis
West, A. Phillip
Joshi, Samit R.
Ueda, Ikuyo
Wilson, Jean
Meng, Hailong
Blevins, Tamara P.
Tsang, Sui
Trentalange, Mark
Siconolfi, Barbara
Park, Koonam
Gill, Thomas M.
Belshe, Robert B.
Kaech, Susan M.
Shadel, Gerald S.
Kleinstein, Steven H.
Shaw, Albert C.
Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
author_facet Thakar, Juilee
Mohanty, Subhasis
West, A. Phillip
Joshi, Samit R.
Ueda, Ikuyo
Wilson, Jean
Meng, Hailong
Blevins, Tamara P.
Tsang, Sui
Trentalange, Mark
Siconolfi, Barbara
Park, Koonam
Gill, Thomas M.
Belshe, Robert B.
Kaech, Susan M.
Shadel, Gerald S.
Kleinstein, Steven H.
Shaw, Albert C.
author_sort Thakar, Juilee
title Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
title_short Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
title_full Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
title_fullStr Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
title_full_unstemmed Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
title_sort aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
description To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age ≥65) adults receiving influenza vaccine in two consecutive seasons and identified those with strong or absent response to vaccine, including a subset of older adults meeting criteria for frailty. PBMCs obtained prior to vaccination (Day 0) and at day 2 or 4, day 7 and day 28 post-vaccine were subjected to gene expression microarray analysis. We defined a response signature and also detected induction of a type I interferon response at day 2 and a plasma cell signature at day 7 post-vaccine in young responders. The response signature was dysregulated in older adults, with the plasma cell signature induced at day 2, and was never induced in frail subjects (who were all non-responders). We also identified a mitochondrial signature in young vaccine responders containing genes mediating mitochondrial biogenesis and oxidative phosphorylation that was consistent in two different vaccine seasons and verified by analyses of mitochondrial content and protein expression. These results represent the first genome-wide transcriptional profiling analysis of age-associated dynamics following influenza vaccination, and implicate changes in mitochondrial biogenesis and function as a critical factor in human vaccine responsiveness.
publisher Impact Journals LLC
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356402/
_version_ 1613197542806257664

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