Coordinate inhibition of M1 macrophage polarization by FIT2-mediated lipid droplet biosynthesis and FABP5

Lipid droplets (LDs) are important organelles involved in host immune response and bacterial infection resistance by recruiting a variety of proteins and antimicrobial peptides with antiviral and antibacterial activities. Macrophage polarization plays an essential role in immune function and lipid metabolism, however, the influence of LDs on macrophage polarization remains unknown. In this study, LD augmentation induced by oleic acid (OA) inhibited M1 polarization in RAW264.7. Since LD budding relies on FIT2 encoded by FITM2, RNA-seq analysis of FITM2 knockdown cells revealed that the reduced LDs impaired the transcriptional level of FABP5, which subsequently regulated LD abundance. Moreover, the influences of FIT2 and FABP5 on LD abundance contributed to the inhibition of M1 macrophage polarization, leading to the impaired capacity of macrophages to resist pathogen infection. Collectively, LD and FABP5 coordinate to inhibit M1 macrophage polarization, which expands our understanding of the role of lipid metabolism in host defense against bacterial infection.