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Charting CNS-endogenous innate immune responses across cells and species

Subject Area Molecular and Cellular Neurology and Neuropathology
Term since 2025
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 559176814
 
As the first line of defense against pathogens, tissue resident cells mount innate immune responses, which varies widely from cell to cell and from species to species. For the central nervous system (CNS) both parenchymal macrophages, called microglia, as well as border macrophages in different compartments (collectively called CNS-associated macrophages, CAM) are key to these local immune reactions to ensure tissue integrity. Remarkably, many risk genes associated with neurodegenerative or autoimmune disorders of the human CNS are found in CNS macrophages. How evolution shaped microglial and CAM responses is currently unclear. We therefore set out to characterize the innate immune responses in different macrophage populations in diverse CNS regions across phylogeny. In detail, we will combine several high-dimensional technologies, such as single-cell RNA-sequencing and time-of-flight mass cytometry with genome-wide single-cell spatial transcriptomics and advanced multiplexing immunohistochemistry to comprehensively characterize the innate immune system at CNS interfaces and parenchyma during homeostasis and perturbation. Immune features will be examined in distinct vertebrate species covering more than 400 million years of evolution. We expect both conserved as well as diverse macrophage response pattern across species and conditions that will provide new insights how the brain’s immune system adapted and evolved.
DFG Programme Priority Programmes
 
 

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