Perception of Ticks and Tick-Borne Diseases Worldwide.

In this comprehensive review study, we addressed the challenge posed by ticks and tick-borne diseases (TBDs) with growing incidence affecting human and animal health worldwide. Data and perspectives were collected from different countries and regions worldwide, including America, Europe, Africa, Asia, and Oceania. The results updated the current situation with ticks and TBD and how it is perceived by society with information bias and gaps. The study reinforces the importance of multidisciplinary and international collaborations to advance in the surveillance, communication and proposed future directions to address these challenges.

Eimeria bovis infection modulates endothelial host cell cholesterol metabolism for successful replication.

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.

Differential inhibition of host cell cholesterol de novo biosynthesis and processing abrogates Eimeria bovis intracellular development.

Eimeria bovis macromeront formation in bovine endothelial host cells is an energy- and nutrient-demanding process. Obligate intracellular replicating coccidians are generally considered as auxotrophic for cholesterol synthesis and scavenge cholesterol from the host cell by either enhancing the uptake of extracellular cholesterol sources or by upregulating the host cellular de novo biosynthesis. We here focused on the latter mechanism and analyzed the effects of several inhibitors targeting the host cellular mevalonate biosynthesis pathway and cholesterol processing. The following inhibitors were used: lovastatin, squalestatin, CI976 and C75 targeting HMG-CoA reductase, squalene synthase, acyl-CoA:cholesterol acyltransferase, and fatty acid synthase, respectively. In summary, all inhibitors significantly interfered with E. bovis meront formation and merozoite production in a dose-dependent manner. Dose effect responses identified lovastatin as the most effective compound, followed by CI976, C75, and squalestatin, respectively. Overall, merozoite production was inhibited by 99.6, 99.7, 84.6, and 70.2% via lovastatin (1 µM), CI976, C75, and squalestatin (all 5 µM) treatments, respectively. Concerning macromeront formation, both the rate and size of developing meronts were affected by inhibitor treatments. The effects were characterized by developmental arrest and meront degradation. In the case of CI976 treatment, we additionally observed detrimental effects on host cellular lipid droplet formation leading to meront developmental arrest irrespective of the time point of treatment onset. These analyses clearly indicate that successful E. bovis intracellular development strictly depends on the host cellular de novo biosynthesis of cholesterol and on the adequate subsequent processing thereof.