Molecular Horizons Seminar - Assistant Professor Alison Scott

We recently reported neutrophil-linked lipid remodelling in a bacterial pulmonary infection model as a possible host-directed therapeutic target. Current studies are delineating the role(s) of specific phagocytic cell subsets in shaping the lipid constituency of the lung parenchyma. In a model of lung neutrophil stimulation, we identified a composite signature of acidic phospholipids that could define neutrophil function on a cell-neighbourhood level of spatial resolution. This functional neutrophil lipid signature in the lung was consistent with pulmonary infection models characterised by dense neutrophil infiltration, such as Pseudomonas aeruginosa. Interestingly, the signature was absent in the macrophage-driven lung response to SARS-CoV-2 infection. These findings instruct our understanding of the spatially distinct lung lipid signatures of phagocyte subsets in multiple mouse infection models of SARS-CoV-2, Bordetella pertussis, Pseudomonas aeruginosa in the context of Cystic Fibrosis, and more. Finally, we are extending these new insights into the phagocytic cell subsets in the brain – specifically microglia in the hippocampus – where competent phagocytosis has a protective role in age-related neurodegeneration. Combined, these results form a lipid signature of functional immune cell subsets that is both spatially sensitive and dependent on tissue context.