title: Eimeria bovis infection modulates endothelial host cell cholesterol metabolism for successful replication.
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.
authors.affiliation: Institute of Parasitology, Biomedical Research Centre, Justus Liebig University Giessen, Schubertstr. 81, D-35392, Giessen, Germany. penny_hamid@ugm.ac.id.
authors.forename: Penny H
authors.initials: PH
authors.lastname: Hamid
authors.affiliation: Institute of Parasitology, Biomedical Research Centre, Justus Liebig University Giessen, Schubertstr. 81, D-35392, Giessen, Germany. Joerg.Hirzmann@vetmed.uni-giessen.de.
authors.forename: Joerg
authors.initials: J
authors.lastname: Hirzmann
authors.affiliation: Institute for Hygiene and Infectious Diseases of Animals, Justus LiebigUniversity Giessen, Frankfurter Str. 85-89, D-35392, Giessen, Germany. Katharina.Kerner@vetmed.uni-giessen.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kerner
authors.affiliation: Institute of Pharmacy and Biochemistry, Department of Biochemistry, Johann-Joachim-Becherweg 30, D-55099, Mainz, Germany. gimpl@uni-mainz.de.
authors.forename: Gerald
authors.initials: G
authors.lastname: Gimpl
authors.affiliation: Institute of Biochemistry, Justus Liebig University Giessen, Friedrichstr. 24, D-35392, Giessen, Germany. Guenter.Lochnit@biochemie.med.uni-giessen.de.
authors.forename: Guenter
authors.initials: G
authors.lastname: Lochnit
authors.affiliation: Institute of Parasitology, Biomedical Research Centre, Justus Liebig University Giessen, Schubertstr. 81, D-35392, Giessen, Germany. Carlos.R.Hermosilla@vetmed.uni-giessen.de.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Hermosilla
authors.affiliation: Institute of Parasitology, Biomedical Research Centre, Justus Liebig University Giessen, Schubertstr. 81, D-35392, Giessen, Germany. Anja.Taubert@vetmed.uni-giessen.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Taubert
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000378:metabolism / Q000469:parasitology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003048:Coccidiosis / Q000378:metabolism / Q000469:parasitology / Q000662:veterinary*; D004539:Eimeria / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism / Q000469:parasitology; D015800:Protozoan Proteins; D015854:Up-Regulation
chemical_list: D015800:Protozoan Proteins; D002784:Cholesterol