Forschungsprojekte (Drittmittel)

Projekt

How does ageing affect the immune response to influenza infections?

The consequences of influenza virus infection are generally more severe in individuals over 65 years of age. 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. In cooperation with the groups of Franklin Toapanta (Maryland, USA), Ted Ross (Pittsburgh, USA), Carlos Guzman (HZI) and Alan Perelson (Los Alamos, USA), we proposed 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 suggested that CD8+ T cells rather than NK cells are most important for adequate viral clearance in young and aged mice. The models predict that the increased levels of pro-inflammatory cytokines associated with “inflammaging” promote slower viral growth in aged mice, which consequently limits the stimulation of immune cells and contributes to the reported impaired responses in the elderly. This result shifts the paradigm of a weaker immune system in the elderly to a weaker viral replication potential in the elderly, which has implications for treatment strategies. These results were derived from mice, and are currently extended to humans.

Mathematical model of influenza virus (V) infection of epithelial cells (U: uninfected, I: infected, R: resistant epithelial cells) and immune response (K: NK cells, T: T cells, various cytokines).…

SIMM members

Nima Amin, Sebastian C. Binder, Alessandro Boianelli (since 2017 in Baden-Württemberg), Kinh Nguyen (since 2017 in Frankfurt am Main), Esteban A. Hernandez-Vargas (since 2017 in Frankfurt am Main)

Publications

Hernandez-Vargas EA, Wilk E, Canini L, Toapanta FR, Binder S, Uvarovskii A, Ross TM, Guzman C, Perelson AS, Meyer-Hermann M. The effects of aging on influenza virus infection dynamics. J Virol 88 (2014) 4123-4131.

Funding

Helmholtz International Graduate School for Infection Research
BMBF - GerontoSys initiative (GerontoShield)
iMED - the Helmholtz Initiative on Personalized Medicine

 

Projektleiter

Beteiligte Gruppen

Geldgeber / Förderer

Sonstige

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