Cytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging.

2.50
HDL Handle:
http://hdl.handle.net/10033/241863
Title:
Cytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging.
Authors:
Cicin-Sain, Luka; Brien, James D; Uhrlaub, Jennifer L; Drabig, Anja; Marandu, Thomas F; Nikolich-Zugich, Janko
Abstract:
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.
Affiliation:
Department of Vaccinology and Applied Microbiology, Helmholtz Center for Infection Research, Braunschweig, Germany.
Citation:
Cytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging. 2012, 8 (8):e1002849 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Aug-2012
URI:
http://hdl.handle.net/10033/241863
DOI:
10.1371/journal.ppat.1002849
PubMed ID:
22916012
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the RG Immunalterung und chronische Infektion (IMCI)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorCicin-Sain, Lukaen_GB
dc.contributor.authorBrien, James Den_GB
dc.contributor.authorUhrlaub, Jennifer Len_GB
dc.contributor.authorDrabig, Anjaen_GB
dc.contributor.authorMarandu, Thomas Fen_GB
dc.contributor.authorNikolich-Zugich, Jankoen_GB
dc.date.accessioned2012-09-07T14:13:36Z-
dc.date.available2012-09-07T14:13:36Z-
dc.date.issued2012-08-
dc.identifier.citationCytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging. 2012, 8 (8):e1002849 PLoS Pathog.en_GB
dc.identifier.issn1553-7374-
dc.identifier.pmid22916012-
dc.identifier.doi10.1371/journal.ppat.1002849-
dc.identifier.urihttp://hdl.handle.net/10033/241863-
dc.description.abstractProminent 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen_GB
dc.titleCytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging.en
dc.typeArticleen
dc.contributor.departmentDepartment of Vaccinology and Applied Microbiology, Helmholtz Center for Infection Research, Braunschweig, Germany.en_GB
dc.identifier.journalPLoS pathogensen_GB

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