Toxoplasma gondii modulates neutral lipid metabolism in macrophage J774 cells

Abstract

The intracellular protozoan Toxoplasma gondii scavenges cholesterol from host cells for its growth. Here, we demonstrated that T. gondii modified neutral lipid metabolism in macrophage cell line J774A.1 cells. Cell-surface expression of low-density lipoprotein receptor (LDLR) and the scavenger receptor SR-A were increased upon T. gondii infection at 40 hours post infection (hpi). In addition, RT-PCR analyses showed that the infection induced the upregulation of hydroxymethylglutaryl-CoA (HMG-CoA) reductase at 20 hpi and ATP-binding cassette, sub-family A (ABC1), member 1 (ABCA1) at 40 hpi. On the other hand, the downregulation of acyl-CoA:cholesterol acyltransferase 1 (ACAT1) and hormone sensitive lipase (HSL) was observed at 40 hpi. Acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) expression increased in both infected and uninfected cells at 40 hpi. Accumulation of lipid bodies and high levels of cellular cholesterol and triacylglycerols (TAG) were observed in J774A.1 cells following T. gondii infection. These results suggest that intracellular cholesterol may be used for T. gondii replication, not for lipid body formation. Our findings support the notion that modulation of the lipid metabolism in host cells is a potential strategy for the treatment and prevention of toxoplasmosis.