The long-term consequences of stroke on systemic immunity

• Applicant: Alba Simats, Ph.D.
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 460809002

Stroke triggers a local neuroinflammatory response that results in an acute and massive infiltration of peripheral immune cells to the brain. Besides this local inflammatory response, stroke also alters peripheral immune homeostasis, which has been shown to have an impact on long-term recovery after stroke and might be a potential cause of secondary comorbidities. The overall objective of this proposal is to understand the long-term systemic consequences of stroke on circulating and tissue-resident myeloid cells. We have demonstrated in our preliminary work that stroke has a long-term impact on circulating myeloid cells as well as on tissue-resident macrophages of vital organs remote from the brain, such as the liver, lung and heart. These novel and preliminary findings are promising to provide new targets for immunological interventions against comorbidities after stroke. Nevertheless, before therapeutic and translational development, open key questions arise from these novel findings, which still need to be addressed. Specifically, I will perform a deep characterization of the peripheral immune landscape by studying the transcriptomic profile at a single cell level of myeloid cells from circulation and vital remote organs chronically after stroke. Next, I will determine the functional implication of stroke on these myeloid cells in vital remote organs by assessing the phagocytic efficiency and the dynamics of myeloid cell turnover. Finally, I will specifically evaluate bone marrow-derived myeloid cells as a potential source of long-term and organism-wide alterations in innate immunity and study whether these circulating cells could be mediating the chronic effects of stroke on organ-specific macrophage populations.

• DFG Programme: WBP Position