The contribution of cytomegalovirus infection to immune senescence is set by the infectious dose

Anke Redeker, Ester B.M. Remmerswaal, Esmé T.I. van der Gracht, Suzanne P.M. Welten, Thomas Höllt, Frits Koning, Luka Cicin-Sain, Janko Nikolich-Zugich, Ineke J.M. ten Berge, René A.W. van Lier, Vincent van Unen, Ramon Arens

Research output: Contribution to journalArticle

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Abstract

The relationship between human cytomegalovirus (HCMV) infections and accelerated immune senescence is controversial. Whereas some studies reported a CMV-associated impaired capacity to control heterologous infections at old age, other studies could not confirm this. We hypothesized that these discrepancies might relate to the variability in the infectious dose of CMV occurring in real life. Here, we investigated the influence of persistent CMV infection on immune perturbations and specifically addressed the role of the infectious dose on the contribution of CMV to accelerated immune senescence. We show in experimental mouse models that the degree of mouse CMV (MCMV)-specific memory CD8+ T cell accumulation and the phenotypic T cell profile are directly influenced by the infectious dose, and data on HCMV-specific T cells indicate a similar connection. Detailed cluster analysis of the memory CD8+ T cell development showed that high-dose infection causes a differentiation pathway that progresses faster throughout the life span of the host, suggesting a virus-host balance that is influenced by aging and infectious dose. Importantly, short-term MCMV infection in adult mice is not disadvantageous for heterologous superinfection with lymphocytic choriomeningitis virus (LCMV). However, following long-term CMV infection the strength of the CD8+ T cell immunity to LCMV superinfection was affected by the initial CMV infectious dose, wherein a high infectious dose was found to be a prerequisite for impaired heterologous immunity. Altogether our results underscore the importance of stratification based on the size and differentiation of the CMV-specific memory T cell pools for the impact on immune senescence, and indicate that reduction of the latent/lytic viral load can be beneficial to diminish CMV-associated immune senescence.

Original languageEnglish (US)
Article number1953
JournalFrontiers in Immunology
Volume8
Issue numberJAN
DOIs
StatePublished - Jan 10 2018

Fingerprint

Cytomegalovirus Infections
T-Lymphocytes
Lymphocytic choriomeningitis virus
Superinfection
Infection
Heterologous Immunity
Infection Control
Viral Load
Cytomegalovirus
Cluster Analysis
Immunity
Theoretical Models
Viruses

Keywords

  • CMV
  • Immunesenesence
  • Memory CD8 T cells
  • Memory inflation
  • Mouse models

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Redeker, A., Remmerswaal, E. B. M., van der Gracht, E. T. I., Welten, S. P. M., Höllt, T., Koning, F., ... Arens, R. (2018). The contribution of cytomegalovirus infection to immune senescence is set by the infectious dose. Frontiers in Immunology, 8(JAN), [1953]. https://doi.org/10.3389/fimmu.2017.01953

The contribution of cytomegalovirus infection to immune senescence is set by the infectious dose. / Redeker, Anke; Remmerswaal, Ester B.M.; van der Gracht, Esmé T.I.; Welten, Suzanne P.M.; Höllt, Thomas; Koning, Frits; Cicin-Sain, Luka; Nikolich-Zugich, Janko; ten Berge, Ineke J.M.; van Lier, René A.W.; van Unen, Vincent; Arens, Ramon.

In: Frontiers in Immunology, Vol. 8, No. JAN, 1953, 10.01.2018.

Research output: Contribution to journalArticle

Redeker, A, Remmerswaal, EBM, van der Gracht, ETI, Welten, SPM, Höllt, T, Koning, F, Cicin-Sain, L, Nikolich-Zugich, J, ten Berge, IJM, van Lier, RAW, van Unen, V & Arens, R 2018, 'The contribution of cytomegalovirus infection to immune senescence is set by the infectious dose', Frontiers in Immunology, vol. 8, no. JAN, 1953. https://doi.org/10.3389/fimmu.2017.01953
Redeker A, Remmerswaal EBM, van der Gracht ETI, Welten SPM, Höllt T, Koning F et al. The contribution of cytomegalovirus infection to immune senescence is set by the infectious dose. Frontiers in Immunology. 2018 Jan 10;8(JAN). 1953. https://doi.org/10.3389/fimmu.2017.01953
Redeker, Anke ; Remmerswaal, Ester B.M. ; van der Gracht, Esmé T.I. ; Welten, Suzanne P.M. ; Höllt, Thomas ; Koning, Frits ; Cicin-Sain, Luka ; Nikolich-Zugich, Janko ; ten Berge, Ineke J.M. ; van Lier, René A.W. ; van Unen, Vincent ; Arens, Ramon. / The contribution of cytomegalovirus infection to immune senescence is set by the infectious dose. In: Frontiers in Immunology. 2018 ; Vol. 8, No. JAN.
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