Abstract
Besnoitia besnoiti, an apicomplexan parasite of cattle being considered as emergent in Europe, replicates fast in host endothelial cells during acute infection and is in considerable need for energy, lipids and other building blocks for offspring formation. Apicomplexa are generally considered as defective in cholesterol synthesis and have to scavenge cholesterol from their host cells for successful replication. Therefore, we here analysed the influence of B. besnoiti on host cellular endogenous cholesterol synthesis and on sterol uptake from exogenous sources. GC-MS-based profiling of cholesterol-related sterols revealed enhanced cholesterol synthesis rates in B. besnoiti-infected cells. Accordingly, lovastatin and zaragozic acid treatments diminished tachyzoite production. Moreover, increased lipid droplet contents and enhanced cholesterol esterification was detected and inhibition of the latter significantly blocked parasite proliferation. Furthermore, artificial increase of host cellular lipid droplet disposability boosted parasite proliferation. Interestingly, lectin-like oxidized low density lipoprotein receptor 1 expression was upregulated in infected endothelial hostcells, whilst low density lipoproteins (LDL) receptor was not affected by parasite infection. However, exogenous supplementations with non-modified and acetylated LDL both boosted B. besnoiti proliferation. Overall, current data show that B. besnoiti simultaneously exploits both, endogenous cholesterol biosynthesis and cholesterol uptake from exogenous sources, during asexual replication.
Highlights
Besnoitia besnoiti is an obligate intracellular apicomplexan parasite which causes bovine besnoitiosis and has a significant economic impact on cattle industry in endemic areas[1]
In this study we focused on two key receptors, LDL receptor (LDLR) and LOX-1, and analysed whether the gene transcription and protein expression of these receptor was influenced by B. besnoiti infections in bovine umbilical vein endothelial cells (BUVEC)
The current data demonstrate that B. besnoiti uses both pathways of cholesterol acquisition when infecting bovine endothelial cells, which correspond to host cells to be infected during the acute phase of cattle besnoitiosis[2,41]
Summary
Besnoitia besnoiti is an obligate intracellular apicomplexan parasite which causes bovine besnoitiosis and has a significant economic impact on cattle industry in endemic areas[1]. Two main routes of cholesterol disposal are provided by potential host cells: endogenous cholesterol de novo synthesis and sterol uptake from extracellular sources via specific receptors These scavenging pathways are differentially exploited by different apicomplexan species. The fact that T. gondii triggers LDL-mediated sterol uptake in CHO cells but not in macrophages, where endogenous de novo synthesis represents the main source of cholesterol[17,35], strengthens the assumption that the mode of cholesterol acquisition may depend on the host cell type. The data show that B. besnoiti infections induce endogenous cholesterol synthesis rates in primary endothelial host cells and profits from enhanced exogenous LDL levels for optimal parasite proliferation
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