CMV infection has been associated with premature immunosenescence and shorter lifespan. To date, no systems-wide analysis for decoupling age from CMV associated changes have been conducted. To address the differences between an immune system in naïve versus CMV infected humans and to decouple the age-related from CMV-related changes, we studied a comprehensive set of assays comprising serum cytokines, cell subset frequencies, whole genome gene expression and various stimulations of immune cells in 30 young and 60 older, CMV seropositive or seronegative individuals. For each measurement we performed a multiple regression analysis on all samples by age, CMV serostatus and the interaction between both variables (age × cmv). We found dramatic differences in multiple measurements of the immune system by age - mostly affecting T cell signaling responses, inflammatory cytokines and many immune-related genes, by CMV - which seems to preferentially modulate the CD4 and B cell compartments at different levels - or when both factors are present with changes mostly restricted to B cell functions. We present, for the first time, a systems immunology view of CMV- and age-associated changes in the immune system.
- Copyright © 2011 by The American Association of Immunologists, Inc.