tetano
Editor, Senior Moderator
J Virol. 2014 Jan 29. [Epub ahead of print]
The effects of aging on influenza virus infection dynamics.
Hernandez-Vargas EA, Wilk E, Canini L, Toapanta FR, Binder S, Uvarovskii A, Ross TM, Guzm?n CA, Perelson AS, Meyer-Hermann M.
Author information
Abstract
Influenza virus infection is a public health problem that is generally more severe in individuals over 65 years of age (elderly). Immunosenescence enhances the susceptibility to viral infections and renders vaccination less effective. Understanding age-related changes in the immune system is crucial in order to design prophylactic and immunomodulatory strategies to reduce morbidity and mortality in the elderly.Here, we propose different mathematical models to provide a quantitative understanding of the immune strategies in the course of influenza virus infection using experimental data from young and aged mice. Simulation results suggest a central role of CD8+ T cells for adequate viral clearance kinetics in young and aged mice. Adding the removal of infected cells by natural killer cells does not improve the fitting either in young or aged animals. We examine the infection resistant state of cells promoted by the cytokines IFN-α/β, IFN-γ and TNF-α separately. The combination of activated CD8+ T cells with either of the cytokines provided the best fit in young and aged animals. During the first 3 days after infection the reproductive number for aged mice is 1.5 fold lower than in young mice (p-value<0.05).IMPORTANCE Fits of our models to experimental data suggest that the increased levels of IFN-α/β, IFN-γ and TNF-α ("inflammaging") promote a slower viral growth in aged mice, which consequently limits the stimulation of immune cells and contributes to the reported impaired responses in the elderly. A quantitative understanding of influenza pathogenesis and its shift in the elderly is the key contribution of this work.
PMID:
24478442
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24478442
The effects of aging on influenza virus infection dynamics.
Hernandez-Vargas EA, Wilk E, Canini L, Toapanta FR, Binder S, Uvarovskii A, Ross TM, Guzm?n CA, Perelson AS, Meyer-Hermann M.
Author information
Abstract
Influenza virus infection is a public health problem that is generally more severe in individuals over 65 years of age (elderly). Immunosenescence enhances the susceptibility to viral infections and renders vaccination less effective. Understanding age-related changes in the immune system is crucial in order to design prophylactic and immunomodulatory strategies to reduce morbidity and mortality in the elderly.Here, we propose different mathematical models to provide a quantitative understanding of the immune strategies in the course of influenza virus infection using experimental data from young and aged mice. Simulation results suggest a central role of CD8+ T cells for adequate viral clearance kinetics in young and aged mice. Adding the removal of infected cells by natural killer cells does not improve the fitting either in young or aged animals. We examine the infection resistant state of cells promoted by the cytokines IFN-α/β, IFN-γ and TNF-α separately. The combination of activated CD8+ T cells with either of the cytokines provided the best fit in young and aged animals. During the first 3 days after infection the reproductive number for aged mice is 1.5 fold lower than in young mice (p-value<0.05).IMPORTANCE Fits of our models to experimental data suggest that the increased levels of IFN-α/β, IFN-γ and TNF-α ("inflammaging") promote a slower viral growth in aged mice, which consequently limits the stimulation of immune cells and contributes to the reported impaired responses in the elderly. A quantitative understanding of influenza pathogenesis and its shift in the elderly is the key contribution of this work.
PMID:
24478442
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24478442