Browsing by Author "Marandu, Thomas F."
Now showing 1 - 5 of 5
Results Per Page
Sort Options
Item 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.Item 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 ReservedItem Mouse CMV Infection Delays Antibody Class Switch upon an Unrelated Virus Challenge(Elsevier, 2014-01) Marandu, Thomas F.; Finsterbusch, Katja; Kröger, Andrea; Cicin-Sain, LukaPoor immune protection upon vaccination is a critical determinant of immunosenescence. Latent Cytomegalovirus (CMV) infection has been associated with poor antibody responses to vaccination, but a causative role for CMV in the poor immune response requires experimental evidence and thus could not be confirmed in clinical studies. To test the hypothesis that latent CMV infection causes poor antibody responses, we infected young or adult mice with mouse CMV and challenged them with vesicular stomatitis virus (VSV) at 15 or 18 months of age. Latent, but not primary infection with mouse CMV resulted in diminished neutralizing titers of the serum IgG fraction at day 7 post challenge, which recovered by day 14 post challenge. This phenomenon was specific for mice infected with mouse CMV, but not mice infected with other herpesviruses, like murine herpesvirus-68 or herpes simplex virus type 1, or mice infected with non-persistent viruses, such as influenza or vaccinia virus. Hence, our data indicate a delay in IgG class-switch that was specific for the CMV infection. Herpesviral infections did not change the B-cell memory compartment, and increased the size of the effector-memory subset of blood CD4 T-cells only when administered in combination. Furthermore, CD4 T-cell response to VSV infection was maintained in latently infected mice. Therefore, our results argue that latent CMV infection impairs B-cell, but not T-cell responses to a challenge with VSV and delays antibody class-switch by a mechanism which may be independent of T-cell help.Item Murine Cytomegalovirus Infection via the Intranasal Route Offers a Robust Model of Immunity Upon Mucosal CMV Infection(2015-11) Oduro, Jennifer D.; Redeker, Anke; Lemmermann, Niels A. W.; Ebermann, Linda; Marandu, Thomas F.; Dekhtiarenko, Iryna; Holzki, Julia K.; Busch, Dirk; Arens, Ramon; Sain, Luka C.Cytomegalovirus (CMV) is a ubiquitous virus, causing the most common congenital infection in humans, yet a vaccine against this virus is not available. The experimental study of immunity against CMV in animal models of infection, such as the infection of mice with the mouse CMV (MCMV), has relied on systemic intraperitoneal infection protocols, although the infection naturally transmits by mucosal routes via body fluids containing CMV. To characterize the biology of infections by mucosal routes, we have compared the kinetics of virus replication, the latent viral load, and CD8 T cell responses in lymphoid organs upon experimental intranasal and intragastric infection to intraperitoneal infection of two unrelated mouse strains. We have observed that intranasal infection induces robust and persistent virus replication in lungs and salivary glands, but a poor one in the spleen. CD8 T cell responses were somewhat weaker than upon intraperitoneal infection, but showed similar kinetic profiles and phenotypes of antigen-specific cells. On the other hand, intragastric infection resulted in abortive or poor virus replication in all tested organs, and poor T cell responses to the virus, especially at late times after infection. Consistent with the T cell kinetics, the MCMV latent load was high in the lungs, but low in the spleen of intranasally infected mice and lowest in all tested organs upon intragastric infection. In conclusion, we show here that intranasal, but not intragastric infection of mice with MCMV represents a robust model to study short and long-term biology of CMV infection by a mucosal routeItem 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.