Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th Street, Hamilton, MT 59840, USA
Benjamin Schwarz
Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th Street, Hamilton, MT 59840, USA
Emily Speranza
Lymphocyte Biology Section, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA; Innate Immunity and Pathogenesis Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, MT, USA
Ian Leighton
Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th Street, Hamilton, MT 59840, USA
Tara Wehrly
Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th Street, Hamilton, MT 59840, USA
Sonja Best
Innate Immunity and Pathogenesis Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, MT, USA
Catharine M. Bosio
Immunity to Pulmonary Pathogens Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, 903 S. 4th Street, Hamilton, MT 59840, USA; Corresponding author
Summary: Resolution of infection results in development of trained innate immunity which is typically beneficial for defense against unrelated secondary infection. Epigenetic changes including modification of histones via binding of various polar metabolites 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 against a third unrelated pathogen. 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.
