Journal
VACCINE
Volume 30, Issue 12, Pages 2060-2067Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2012.01.015
Keywords
Older adults; Elderly; Influenza; Influenza vaccine; Granzyme B; Inflammation; CMV
Categories
Funding
- Canadian Institutes of Health Research [FRN-89729]
- US National Institute of Allergy and Infectious Diseases
- BC Lung Association
- GlaxoSmithKline
- Merck Frosst
- Merck
- Sanofi Pasteur
- Protein Sciences
- Deutsche Forschungsgemeinschaft (DFG) [PA 361/14-1]
- Bundesministerium fur Bildung und Forschung (BMBF) [0315890F]
- European Commission [259679]
- National Institutes of Health [R01 AI68265, U01 AI074449]
- National Institute of Allergy and Infectious Diseases
- Network of Centres of Excellence in Vaccines and Immunotherapeutics (CANVAC) in Canada
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Influenza remains the single most important cause of excess disability and mortality during the winter months. In spite of widespread influenza vaccination programs leading to demonstrated cost-savings in the over 65 population, hospitalization and death rates for acute respiratory illnesses continue to rise. As a person ages, increased serum levels of inflammatory cytokines are commonly recorded (TNF-alpha, IL-1, IL-6). Termed inflammaging, this has been linked to persistent cytomegalovirus (CMV) infection and immune senescence, while increased anti-inflammatory cytokines (IL-10, TGF-beta) are possibly associated with more healthy aging. Paradoxically, a shift with aging toward an anti-inflammatory (IL-10) response and decline in the IFN=gamma:IL-10 ratio in influenza-challenged peripheral blood mononuclear cells is associated with a decline in the cytolytic capacity of CD8+ T cells responsible for clearing influenza virus from infected lung tissue. Thus, it is seemingly counter intuitive that the immune phenotype of healthy aging predicts a poor cell-mediated immune response and more serious outcomes of influenza. Herein we postulate a mechanistic link between the accumulation of late-stage, potentially terminally differentiated T cells, many or most of which result from CMV infection, and the immunopathogenesis of influenza infection, mediated by granzyme B in older adults. Further, adjuvanted influenza vaccines that stimulate inflammatory cytokines and suppress the IL-10 response to influenza challenge, would be expected to enhance protection in the 65+ population. (C) 2012 Elsevier Ltd. All rights reserved.
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