Coordinated inhibition of M1 macrophage polarization by FIT2-mediated lipid droplet biosynthesis and FABP5OACSCDCSTPCD
Lipid droplets(LDs)serve as dynamic organelles central to host immune response and bacterial infection resistance by recruiting multiple proteins and peptides with established antiviral and antibacterial properties.Although macrophage polarization is integral to both innate immunity and lipid homeostasis,the regulatory influence of LDs on this process remains unclear.In this study,augmentation of LDs via oleic acid(OA)treatment attenuated M1 polarization in RAW264.7 macrophages.Given that LD budding is mediated by fat storage-inducing transmembrane protein 2(FIT2)encoded by FITM2,transcriptomic analysis following FITM2 knockdown revealed suppressed expression of fatty acid-binding protein 5(FABP5),a lipid-binding protein that further modulated LD abundance.Both FIT2 and FABP5 were found to regulate LD content and collectively contributed to inhibition of M1 macrophage polarization.This shift impaired macrophage capacity to mount effective antibacterial responses.These findings identify a coordinated role for LDs and FABP5 in modulating M1 macrophage polarization,establishing a mechanistic link between lipid metabolism and innate host defense against bacterial infection.
Yi-Han Liu;Bei Li;Yuan-Xing Zhang;Sang Ho Choi;Shuai Shao;Qi-Yao Wang
State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,ChinaState Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,ChinaLaboratory of Aquatic Animal Diseases of MARA,Shanghai 200237,China Shanghai Engineering Research Center of Maricultured Animal Vaccines,Shanghai 200237,ChinaNational Research Laboratory of Molecular Microbiology and Toxicology,Department of Agricultural Biotechnology,Seoul National University,Seoul 151-742,Republic of KoreaState Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China Laboratory of Aquatic Animal Diseases of MARA,Shanghai 200237,China Shanghai Engineering Research Center of Maricultured Animal Vaccines,Shanghai 200237,ChinaState Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China Laboratory of Aquatic Animal Diseases of MARA,Shanghai 200237,China Shanghai Engineering Research Center of Maricultured Animal Vaccines,Shanghai 200237,China
医药卫生
Macrophage polarizationLipid dropletFABP5FIT2
《Zoological Research》 2025 (5)
P.1175-1186,12
supported by the National Key Research and Development Program(2022YFE0101200)National Natural Science Foundation of China(32130108)China Agriculture Research System of MOF and MARA(CARS-47)。
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