Browsing by Author "Zugich, Janko N."

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    Cytomegalovirus Infection Impairs Immune Responses and Accentuates T-Cell Pool Changes Observed in Mice With Aging
    (2012-07) Cicin-Sain, Luka; Brien, James D.; Uhrlaub, Jennifer L.; Drabig, Anja; Marandu, Thomas F.; Zugich, Janko N.
    Prominent immune alterations associated with aging include the loss of naïve T-cell numbers, diversity and function. While genetic contributors and mechanistic details in the aging process have been addressed in multiple studies, the role of environmental agents in immune aging remains incompletely understood. From the standpoint of environmental infectious agents, latent cytomegalovirus (CMV) infection has been associated with an immune risk profile in the elderly humans, yet the cause-effect relationship of this association remains unclear. Here we present direct experimental evidence that mouse CMV (MCMV) infection results in select T-cell subset changes associated with immune aging, namely the increase of relative and absolute counts of CD8 T-cells in the blood, with a decreased representation of the naïve and the increased representation of the effector memory blood CD8 T-cells. Moreover, MCMV infection resulted in significantly weaker CD8 responses to superinfection with Influenza, Human Herpes Virus I or West-Nile-Virus, even 16 months following MCMV infection. These irreversible losses in T-cell function could not be observed in uninfected or in vaccinia virus-infected controls and were not due to the immune-evasive action of MCMV genes. Rather, the CD8 activation in draining lymph nodes upon viral challenge was decreased in MCMV infected mice and the immune response correlated directly to the frequency of the naïve and inversely to that of the effector cells in the blood CD8 pool. Therefore, latent MCMV infection resulted in pronounced changes of the T-cell compartment consistent with impaired naïve T-cell function.
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    Immune Protection against Virus Challenge in Aging Mice Is Not Affected By Latent Herpesviral Infections
    (2015-09) Marandu, Thomas F.; Oduro, Jennifer D.; Borkner, Lisa; Dekhtiarenko, Iryna; Uhrlaub, Jennifer; Drabig, Anja; Kröger, Andrea; Zugich, Janko N.; Sain, Luka C.
    Latent herpesvirus infections alter the immune homeostasis. To understand if this results in aging-related loss of immune protection against emerging infections, we challenged old mice carrying latent mouse CMV, HSV-1 and/or MHV-68 with Influenza, WNV or VSV. We observed no increase in mortality or weight-loss over herpesvirus-negative counterparts and a relative, but no absolute reduction in CD8 responses against acute infections. Therefore, herpesviruses do not appear to increase susceptibility to emerging infections in aging. Copyright © 2015, American Society for Microbiology. All Rights Reserved
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    New Advances in CMV and Immunosenescence
    (Elsevier, 2014-04) Sansoni, Paolo; Vescovini, Rosanna; Fagnoni, Francesco; Akbar, Arne; Arens, Ramon; Chiu, Yen L.; Šain, Luka Č.; Merville, Julie D.; Derhovanessian, Evelyna; Martinez, Sara F.; Franceschi, Claudio; Frasca, Daniela; Fulöp, Tamas; Furman, David; Klotsas, Effrossyni G.; Goodrum, Felicia; Loebenstein, Beatrix G.; Hurme, Mikko; Kern, Florian; Liller, Daniele; Botet, Miguel L.; Maier, Andrea B.; Marandu, Thomas F.; Marchant, Arnaud; Matheï, Catharina; Moss, Paul; Muntasell, Aura; Remmerswaal, Ester B.M.; Riddell, Natalie E.; Rothe, Kathrin; Sauce, Delphine; Shin, Eui C.; Simanek, Amanda M.; Smithey, Megan J.; Nauclér, Cecilia S.; Solana, Rafael; Thomas, Paul G; Lier, Rene V.; Pawelec, Graham; Zugich, Janko N.
    Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and with several age-related diseases. However, current evidence on whether and how human CMV (HCMV) infection is implicated in immunosenescence and in age-related diseases remains incomplete and many aspects of CMV involvement in immune aging remain controversial. The attendees of the 4th International Workshop on "CMV & Immunosenescence", held in Parma, Italy, 25-27th March, 2013, presented and discussed data related to these open questions, which are reported in this commentary.