Pulmonary Infection Induces Scarred Lipidome Influencing Trained Immunity

Resolution of infection results in development of trained innate immunity which is typically beneficial for the host in defense against unrelated secondary infection. Epigenetic changes underlie the establishment of trained innate immunity therefore host metabolism and this response are intimately linked. However, little is known regarding the influence of lipids on the development and function of trained immunity. Utilizing two models of pulmonary bacterial infection combined with multi-omic approaches, we identified persistent, pathogen-specific changes to the lung lipidome that correlated with differences in the trained immune response. Further, we establish the specific cellular populations in the lung that contribute to this altered lipidome. Together these results expand our understanding of the pulmonary trained innate immune response and the contributions of host lipids in informing that response.