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The interplay between immune maturation, age, chronic viral infection and environment
BACKGROUND: The worldwide increase in life expectancy has been associated with an increase in age-related morbidities. The underlying mechanisms resulting in immunosenescence are only incompletely understood. Chronic viral infections, in particular infection with human cytomegalovirus (HCMV), have b...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436863/ https://www.ncbi.nlm.nih.gov/pubmed/25991918 http://dx.doi.org/10.1186/s12979-015-0030-3 |
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author | Oxford, Kristie L dela Pena-Ponce, Myra Grace A Jensen, Kara Eberhardt, Meghan K Spinner, Abigail Van Rompay, Koen KA Rigdon, Joseph Mollan, Katie R Krishnan, VV Hudgens, Michael G Barry, Peter A De Paris, Kristina |
author_facet | Oxford, Kristie L dela Pena-Ponce, Myra Grace A Jensen, Kara Eberhardt, Meghan K Spinner, Abigail Van Rompay, Koen KA Rigdon, Joseph Mollan, Katie R Krishnan, VV Hudgens, Michael G Barry, Peter A De Paris, Kristina |
author_sort | Oxford, Kristie L |
collection | PubMed |
description | BACKGROUND: The worldwide increase in life expectancy has been associated with an increase in age-related morbidities. The underlying mechanisms resulting in immunosenescence are only incompletely understood. Chronic viral infections, in particular infection with human cytomegalovirus (HCMV), have been suggested as a main driver in immunosenescence. Here, we propose that rhesus macaques could serve as a relevant model to define the impact of chronic viral infections on host immunity in the aging host. We evaluated whether chronic rhesus CMV (RhCMV) infection, similar to HCMV infection in humans, would modulate normal immunological changes in the aging individual by taking advantage of the unique resource of rhesus macaques that were bred and raised to be Specific Pathogen Free (SPF-2) for distinct viruses. RESULTS: Our results demonstrate that normal age-related immunological changes in frequencies, activation, maturation, and function of peripheral blood cell lymphocytes in humans occur in a similar manner over the lifespan of rhesus macaques. The comparative analysis of age-matched SPF-2 and non-SPF macaques that were housed under identical conditions revealed distinct differences in certain immune parameters suggesting that chronic pathogen exposure modulated host immune responses. All non-SPF macaques were infected with RhCMV, suggesting that chronic RhCMV infection was a major contributor to altered immune function in non-SPF macaques, although a causative relationship was not established and outside the scope of these studies. Further, we showed that immunological differences between SPF-2 and non-SPF macaques were already apparent in adolescent macaques, potentially predisposing RhCMV-infected animals to age-related pathologies. CONCLUSIONS: Our data validate rhesus macaques as a relevant animal model to study how chronic viral infections modulate host immunity and impact immunosenescence. Comparative studies in SPF-2 and non-SPF macaques could identify important mechanisms associated with inflammaging and thereby lead to new therapies promoting healthy aging in humans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12979-015-0030-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4436863 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44368632015-05-20 The interplay between immune maturation, age, chronic viral infection and environment Oxford, Kristie L dela Pena-Ponce, Myra Grace A Jensen, Kara Eberhardt, Meghan K Spinner, Abigail Van Rompay, Koen KA Rigdon, Joseph Mollan, Katie R Krishnan, VV Hudgens, Michael G Barry, Peter A De Paris, Kristina Immun Ageing Research BACKGROUND: The worldwide increase in life expectancy has been associated with an increase in age-related morbidities. The underlying mechanisms resulting in immunosenescence are only incompletely understood. Chronic viral infections, in particular infection with human cytomegalovirus (HCMV), have been suggested as a main driver in immunosenescence. Here, we propose that rhesus macaques could serve as a relevant model to define the impact of chronic viral infections on host immunity in the aging host. We evaluated whether chronic rhesus CMV (RhCMV) infection, similar to HCMV infection in humans, would modulate normal immunological changes in the aging individual by taking advantage of the unique resource of rhesus macaques that were bred and raised to be Specific Pathogen Free (SPF-2) for distinct viruses. RESULTS: Our results demonstrate that normal age-related immunological changes in frequencies, activation, maturation, and function of peripheral blood cell lymphocytes in humans occur in a similar manner over the lifespan of rhesus macaques. The comparative analysis of age-matched SPF-2 and non-SPF macaques that were housed under identical conditions revealed distinct differences in certain immune parameters suggesting that chronic pathogen exposure modulated host immune responses. All non-SPF macaques were infected with RhCMV, suggesting that chronic RhCMV infection was a major contributor to altered immune function in non-SPF macaques, although a causative relationship was not established and outside the scope of these studies. Further, we showed that immunological differences between SPF-2 and non-SPF macaques were already apparent in adolescent macaques, potentially predisposing RhCMV-infected animals to age-related pathologies. CONCLUSIONS: Our data validate rhesus macaques as a relevant animal model to study how chronic viral infections modulate host immunity and impact immunosenescence. Comparative studies in SPF-2 and non-SPF macaques could identify important mechanisms associated with inflammaging and thereby lead to new therapies promoting healthy aging in humans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12979-015-0030-3) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-09 /pmc/articles/PMC4436863/ /pubmed/25991918 http://dx.doi.org/10.1186/s12979-015-0030-3 Text en © Oxford et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Oxford, Kristie L dela Pena-Ponce, Myra Grace A Jensen, Kara Eberhardt, Meghan K Spinner, Abigail Van Rompay, Koen KA Rigdon, Joseph Mollan, Katie R Krishnan, VV Hudgens, Michael G Barry, Peter A De Paris, Kristina The interplay between immune maturation, age, chronic viral infection and environment |
title | The interplay between immune maturation, age, chronic viral infection and environment |
title_full | The interplay between immune maturation, age, chronic viral infection and environment |
title_fullStr | The interplay between immune maturation, age, chronic viral infection and environment |
title_full_unstemmed | The interplay between immune maturation, age, chronic viral infection and environment |
title_short | The interplay between immune maturation, age, chronic viral infection and environment |
title_sort | interplay between immune maturation, age, chronic viral infection and environment |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436863/ https://www.ncbi.nlm.nih.gov/pubmed/25991918 http://dx.doi.org/10.1186/s12979-015-0030-3 |
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