title: The interplay between immune maturation, age, chronic viral infection and environment.
abstract: 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.
authors.affiliation: Center of Comparative Medicine, University of California, Davis, California USA.
authors.forename: Kristie L
authors.initials: KL
authors.lastname: Oxford
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina, Burnett-Womack Bldg, 160 Dental Circle, Chapel Hill, NC 27599-7292 USA.
authors.forename: Myra Grace A
authors.initials: MGA
authors.lastname: Dela Pena-Ponce
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina, Burnett-Womack Bldg, 160 Dental Circle, Chapel Hill, NC 27599-7292 USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Jensen
authors.affiliation: Center of Comparative Medicine, University of California, Davis, California USA.
authors.forename: Meghan K
authors.initials: MK
authors.lastname: Eberhardt
authors.affiliation: California National Primate Research Center, University of California, Davis, California USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Spinner
authors.affiliation: California National Primate Research Center, University of California, Davis, California USA.
authors.forename: Koen Ka
authors.initials: KK
authors.lastname: Van Rompay
authors.affiliation: Gillings School of Public Health, University of North Carolina, Chapel Hill, North Carolina USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Rigdon
authors.affiliation: Gillings School of Public Health, University of North Carolina, Chapel Hill, North Carolina USA.|Center for AIDS Research, University of North Carolina, Chapel Hill, North Carolina USA.
authors.forename: Katie R
authors.initials: KR
authors.lastname: Mollan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Davis, California USA.
authors.forename: V V
authors.initials: VV
authors.lastname: Krishnan
authors.affiliation: Gillings School of Public Health, University of North Carolina, Chapel Hill, North Carolina USA.|Center for AIDS Research, University of North Carolina, Chapel Hill, North Carolina USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.affiliation: Center of Comparative Medicine, University of California, Davis, California USA.|California National Primate Research Center, University of California, Davis, California USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Barry
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina, Burnett-Womack Bldg, 160 Dental Circle, Chapel Hill, NC 27599-7292 USA.|Center for AIDS Research, University of North Carolina, Chapel Hill, North Carolina USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: De Paris
keywords: Aging; Immune development and maturation; Immune maturation and function; Inflammaging; RhCMV infection; Rhesus CMV infection; Rhesus macaques