The interplay between immune maturation, age, chronic viral infection and environment
| Autor: | Abigail Spinner, Myra Grace Dela Pena-Ponce, Kristina De Paris, Kristie L. Oxford, Meghan K. Eberhardt, Michael G. Hudgens, Koen K. A. Van Rompay, Katie R. Mollan, Viswanathan V Krishnan, Joseph Rigdon, Peter A. Barry, Kara Jensen |
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| Rok vydání: | 2015 |
| Předmět: |
Human cytomegalovirus
Aging animal diseases Clinical Sciences Immunology Immune development and maturation Viral infection 03 medical and health sciences 0302 clinical medicine Immune system medicine 2.2 Factors relating to the physical environment 2.1 Biological and endogenous factors Peripheral blood cell Aetiology Immune maturation and function Pathogen 030304 developmental biology Specific-pathogen-free 0303 health sciences Rhesus CMV infection Rhesus macaques biology Inflammatory and immune system Research Immunosenescence biochemical phenomena metabolism and nutrition medicine.disease Inflammaging Virology 3. Good health Ageing Infectious Diseases Good Health and Well Being biology.protein HIV/AIDS Antibody Infection RhCMV infection 030215 immunology |
| Zdroj: | Immunity & ageing : I & A, vol 12, iss 1 Immunity & Ageing : I & A |
| ISSN: | 1742-4933 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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