Abstract
BackgroundThe 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.ResultsOur 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.ConclusionsOur 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 materialThe online version of this article (doi:10.1186/s12979-015-0030-3) contains supplementary material, which is available to authorized users.
Highlights
The worldwide increase in life expectancy has been associated with an increase in age-related morbidities
We tested whether non-SPF macaques underwent similar changes in immune populations with age, and whether altered immune parameters could be correlated to rhesus CMV (RhCMV) infection status
Previous seroepidemiological and molecular studies have demonstrated that infants born to non-SPF dams during the first year of life are increasingly likely to become infected with RhCMV, simian foamy virus (SFV), and rhesus rhadinovirus (RRV) due to repeated exposure of bodily fluids containing infectious virus particles
Summary
The worldwide increase in life expectancy has been associated with an increase in age-related morbidities. 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. A unifying link between the higher rates of these disparate diseases observed in aging populations is the progressive decline in immune functions. A central driving force in the decline of immune function is the inherent process of progressive thymic involution, which results in an extremely restricted generation of naïve T cells by the fifth or sixth decades of life. Studies over the past several years have emphasized the critical importance of extrinsic factors, which when layered over thymic involution, can further enhance immune dysfunction and thereby increase the rates of morbidity and mortality in aging individuals
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