Abstract
During first merogony Eimeria bovis forms large macromeronts in endothelial host cells containing >120 000 merozoites I. During multiplication, large amounts of cholesterol are indispensable for the enormous offspring membrane production. Cholesterol auxotrophy was proven for other apicomplexan parasites. Consequently they scavenge cholesterol from their host cell apparently in a parasite-specific manner. We here analyzed the influence of E. bovis infection on endothelial host cell cholesterol metabolism and found considerable differences to other coccidian parasites. Overall, free cholesterol significantly accumulated in E. bovis infected host cells. Furthermore, a striking increase of lipid droplet formation was observed within immature macromeronts. Artificial host cell lipid droplet enrichment significantly improved E. bovis merozoite I production confirming the key role of lipid droplet contents for optimal parasite proliferation. The transcription of several genes being involved in both, cholesterol de novo biosynthesis and low density lipoprotein-(LDL) mediated uptake, was significantly up-regulated at a time in infected cells suggesting a simultaneous exploitation of these two cholesterol acquisition pathways. E. bovis scavenges LDL-derived cholesterol apparently through significantly increased levels of surface LDL receptor abundance and LDL binding to infected cells. Consequently, LDL supplementation significantly improved parasite replication. The up-regulation of the oxidized LDL receptor 1 furthermore identified this scavenger receptor as a key molecule in parasite-triggered LDL uptake. Moreover, cellular cholesterol processing was altered in infected cells as indicated by up-regulation of cholesterol-25-hydroxylase and sterol O-acyltransferase. Overall, these results show that E. bovis considerably exploits the host cell cholesterol metabolism to guarantee its massive intracellular growth and replication.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-015-0230-z) contains supplementary material, which is available to authorized users.
Highlights
Eimeria bovis represents one of the most pathogenic Eimeria species causing cattle coccidiosis [1]
In contrast to macrophages [10], T. gondii exclusively utilized cholesterol derived from internalized Low density lipoprotein (LDL) particles in CHO cells [4] whilst transcriptomic data on infected fibroblasts indicated an up-regulation of molecules being involved in the mevalonate pathway [11]
Given that LDL binding and LDL receptor (LDLR) surface expression is enhanced in E. bovis-infected host cells, we investigated whether exogenous LDL supplementation would be of benefit for E. bovis macromeront development in vitro
Summary
Eimeria bovis represents one of the most pathogenic Eimeria species causing cattle coccidiosis [1]. Cholesterol auxotrophy was reported for Toxoplasma gondii and Cryptosporidium parvum [4,7,9]. In consequence these parasites scavenge cholesterol from their host cell thereby exploiting different cellular pathways. Hamid et al Veterinary Research (2015) 46:100 different strategies were described in different T. gondii-infected host cell types. Cholesterol is inserted in the parasite plasma membrane, the parasitophorous vacuolar membrane (PVM), sequestered in cholesterol-rich organelles in T. gondii-infected host cells and is esterified for lipid droplet deposition [4,12,13,14]. T. gondii infection leads to enhanced cytoplasmic lipid droplet formation in skeletal muscle cell cultures [16]
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