Functional role of neuronal ageing on neuron-T cell interaction during viral CNS infection

Our society is an ageing one with both cognitive decline and impairments in immune response of varying severities and causalities affecting individuals and family alike. Especially, the increasing susceptibility of the elderly to viral infections cause increasing problems for individuals and for the society as a whole. Here, we will investigate the impact and functional role of neuronal ageing on neuron-T cell interaction during neurotropic viral infection. New cultivation techniques for neurons mimicking neuronal ageing, which also take viscoelastic properties of the ageing brain into account, will be used in addition to in vivo cell type-selective metabolic proteome labeling. Within these systems we aim to explore the molecular and crucially intra- and intercellular mechanisms underlying the increased susceptibility to neuronal infections in the elderly. The focus is laid on how ageing of neurons impacts signal transduction and activation in neurons themselves as well as in antigen-specific CD8⁺ T cells. Furthermore, the interaction of neurons and T cells shall be investigated in vivo under pathophysiological conditions via systemic infection with neurotropic Langat virus, an attenuated member of the Tick-borne encephalitis 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 both in vitro and in vivo.