Functional role of neuronal ageing on neuron-T cell interaction during viral CNS infection.
Die Rolle des neuronalen Alterns auf die Neuron-T Zell Interaktion bei viralen Infektionen des zentralen Nervensystems.
Morbidity and mortality associated with viral infections such as tick-borne encephalitis virus (TBEV) increase with age. Declining immune responses, increased inflammatory responses and dysbalances in the innate antiviral response of the elderly lead accompany changes in neuronal morphology, loss of neuronal functionality and increased neuronal cell death during viral infections. Our main aim is to characterize the interface between the immune response and the aging neuronal population. The aim is to investigate the impact and functional role of neuronal ageing on neuron-T cell interaction during neurotropic viral infection. Using new cultivation techniques mimicking neuronal ageing in vitro and in vivo cell type-selective metabolic proteome labeling molecular and crucially intra- and intercellular mechanisms of increased susceptibility of neuronal infections will be determined in neurons themselves and in specific T cells. Furthermore, the interaction of neurons and T cells will be investigated in vivo under pathophysiological conditions by systemic infection with neurotropic Langat virus. Collectively, the project will shed important insights into the molecular dynamics regulating the age-dependent interplay of the immune system with the nervous system.