TY - JOUR
T1 - The shifting lipidomic landscape of blood monocytes and neutrophils during pneumonia
AU - Schuurman, Alex R.
AU - Chouchane, Osoul
AU - Butler, Joe M.
AU - Peters-Sengers, Hessel
AU - Joosten, Sebastiaan
AU - Brands, Xanthe
AU - Haak, Bastiaan W.
AU - Otto, Natasja A.
AU - Uhel, Fabrice
AU - Klarenbeek, Augustijn
AU - van Linge, Christine C. A.
AU - van Kampen, Antoine
AU - Pras-Raves, Mia
AU - van Weeghel, Michel
AU - van Eijk, Marco
AU - Ferraz, Maria J.
AU - Faber, Daniël R.
AU - de Vos, Alex
AU - Scicluna, Brendon P.
AU - Vaz, Frédéric M.
AU - Wiersinga, W. Joost
AU - van der Poll, Tom
N1 - Publisher Copyright: © 2024, Schuurman et al.
PY - 2024
Y1 - 2024
N2 - The lipidome of immune cells during infection has remained unexplored, although evidence of the importance of lipids in the context of immunity is mounting. In this study, we performed untargeted lipidomic analysis of blood monocytes and neutrophils from patients hospitalized for pneumonia and age- and sex-matched noninfectious control volunteers. We annotated 521 and 706 lipids in monocytes and neutrophils, respectively, which were normalized to an extensive set of internal standards per lipid class. The cellular lipidomes were profoundly altered in patients, with both common and distinct changes between the cell types. Changes involved every level of the cellular lipidome: differential lipid species, class-wide shifts, and altered saturation patterns. Overall, differential lipids were mainly less abundant in monocytes and more abundant in neutrophils from patients. One month after hospital admission, lipidomic changes were fully resolved in monocytes and partially in neutrophils. Integration of lipidomic and concurrently collected transcriptomic data highlighted altered sphingolipid metabolism in both cell types. Inhibition of ceramide and sphingosine-1-phosphate synthesis in healthy monocytes and neutrophils resulted in blunted cytokine responses upon stimulation with lipopolysaccharide. These data reveal major lipidomic remodeling in immune cells during infection, and link the cellular lipidome to immune functionality.
AB - The lipidome of immune cells during infection has remained unexplored, although evidence of the importance of lipids in the context of immunity is mounting. In this study, we performed untargeted lipidomic analysis of blood monocytes and neutrophils from patients hospitalized for pneumonia and age- and sex-matched noninfectious control volunteers. We annotated 521 and 706 lipids in monocytes and neutrophils, respectively, which were normalized to an extensive set of internal standards per lipid class. The cellular lipidomes were profoundly altered in patients, with both common and distinct changes between the cell types. Changes involved every level of the cellular lipidome: differential lipid species, class-wide shifts, and altered saturation patterns. Overall, differential lipids were mainly less abundant in monocytes and more abundant in neutrophils from patients. One month after hospital admission, lipidomic changes were fully resolved in monocytes and partially in neutrophils. Integration of lipidomic and concurrently collected transcriptomic data highlighted altered sphingolipid metabolism in both cell types. Inhibition of ceramide and sphingosine-1-phosphate synthesis in healthy monocytes and neutrophils resulted in blunted cytokine responses upon stimulation with lipopolysaccharide. These data reveal major lipidomic remodeling in immune cells during infection, and link the cellular lipidome to immune functionality.
UR - http://www.scopus.com/inward/record.url?scp=85185843233&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.164400
DO - 10.1172/jci.insight.164400
M3 - Article
C2 - 38385743
SN - 2379-3708
VL - 9
JO - JCI Insight
JF - JCI Insight
IS - 4
M1 - e164400
ER -