Oleic acid upregulates the expression of perilipin 2 enhancing macrophage clearance of Mycobacterium tuberculosis
Objective:To investigate the role of oleic acid(OA)in the clearance of Mycobacterium tuberculosis(MTB)by macrophages and explore the underlying mechanisms.Methods:Macrophages induced from the human monocyte leukemia cell line(THP-1)were infected with the standard MTB strain H37Ra with or without oleic acid.The effect of oleic acid on the clearance of MTB by macrophages was assessed using colony-forming unit(CFU).Key target genes were identified through RNA-seq,and relevant pathways were determined using gene enrichment analysis.Real-time quantitative PCR was used for validating gene expression.Results:After 72 hours of infection with H37Ra,the CFU for macrophages(H37Ra group)was 49×104(48×104,59×104),significantly higher than that of macrophages induced with oleic acid(OA+H37Ra group)at 34×104(30×104,42×104)(U=3.500,P=0.017).RNA-seq data showed that the expression of recombinant perilipin 2(PLIN2)in the OA+H37Ra group was significantly higher than in the H37Ra group.In oleic acid-induced macrophages,the CFU in the PLIN2 knock down group was 86×104(78×104,96×104),significantly higher than that in the control group(56×104(54×104,62×104);U=3.000,P=0.015).In the OA+H37Ra group,the relative expression of PLIN2 was 3.219±0.298,significantly higher than the 0.555±0.028 in the H37Ra group(t=15.410,P＜0.01).The relative expression of PPARy in the OA+H37Ra group was 0.666±0.075,significantly lower than the 2.217±0.153 in the H37Ra group(t=14.700,P＜0.01).In the OA+H37Ra group,the relative expression of ACOX1 and HADHA was 1.410±0.124 and 1.107±0.111,both significantly lower than the H37Ra group of 2.476±0.207 and 3.140±0.240(t=13.520,P＜0.01;t=12.760,P＜0.01)respectively.Conclusion:Oleic acid regulates fatty acid oxidation in macrophages through the lipid droplet surface protein PLIN2,promoting the clearance of MTB by macrophages.
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