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      Microarray-based transcriptional profiling of Eimeria bovis-infected bovine endothelial host cells

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          Abstract

          Within its life cycle Eimeria bovis undergoes a long lasting intracellular development into large macromeronts in endothelial cells. Since little is known about the molecular basis of E. bovis-triggered host cell regulation we applied a microarray-based approach to define transcript variation in bovine endothelial cells early after sporozoite invasion (4 h post inoculation (p.i.)), during trophozoite establishment (4 days p.i.), during early parasite proliferation (8 days p.i.) and towards macromeront maturation (14 days p.i.). E. bovis infection led to significant changes in the abundance of many host cell gene transcripts. As infection progressed, the number of regulated genes increased such that 12, 45, 175 and 1184 sequences were modulated at 4 h, 4, 8 and 14 days p.i., respectively. These genes significantly interfered with several host cell functions, networks and canonical pathways, especially those involved in cellular development, cell cycle, cell death, immune response and metabolism. The correlation between stage of infection and the number of regulated genes involved in different aspects of metabolism suggest parasite-derived exploitation of host cell nutrients. The modulation of genes involved in cell cycle arrest and host cell apoptosis corresponds to morphological in vitro findings and underline the importance of these aspects for parasite survival. Nevertheless, the increasing numbers of modulated transcripts associated with immune responses also demonstrate the defensive capacity of the endothelial host cell. Overall, this work reveals a panel of novel candidate genes involved in E. bovis-triggered host cell modulation, providing a valuable tool for future work on this topic.

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          Most cited references32

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          CDK inhibitors: positive and negative regulators of G1-phase progression.

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            Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome.

            The cellular-stress response can mediate cellular protection through expression of heat-shock protein (Hsp) 70, which can interfere with the process of apoptotic cell death. Stress-induced apoptosis proceeds through a defined biochemical process that involves cytochrome c, Apaf-1 and caspase proteases. Here we show, using a cell-free system, that Hsp70 prevents cytochrome c/dATP-mediated caspase activation, but allows the formation of Apaf-1 oligomers. Hsp70 binds to Apaf-1 but not to procaspase-9, and prevents recruitment of caspases to the apoptosome complex. Hsp70 therefore suppresses apoptosis by directly associating with Apaf-1 and blocking the assembly of a functional apoptosome.
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              Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids.

              The merozoite stage of the malaria parasite that infects erythrocytes and causes the symptoms of the disease is initially formed inside host hepatocytes. However, the mechanism by which hepatic merozoites reach blood vessels (sinusoids) in the liver and escape the host immune system before invading erythrocytes remains unknown. Here, we show that parasites induce the death and the detachment of their host hepatocytes, followed by the budding of parasite-filled vesicles (merosomes) into the sinusoid lumen. Parasites simultaneously inhibit the exposure of phosphatidylserine on the outer leaflet of host plasma membranes, which act as "eat me" signals to phagocytes. Thus, the hepatocyte-derived merosomes appear to ensure both the migration of parasites into the bloodstream and their protection from host immunity.
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                Author and article information

                Journal
                Vet Res
                vetres
                Veterinary Research
                EDP Sciences
                0928-4249
                1297-9716
                12 July 2010
                Sep-Oct 2010
                : 41
                : 5 ( publisher-idID: vetres/2010/05 )
                : 70
                Affiliations
                [1 ] Institute of Parasitology, Justus Liebig University Giessen Rudolf-Buchheim-Str. 2 35392 Giessen Germany
                [2 ] Research Institute for the Biology of Farm Animals, Research Unit ‘Molecular Biology’ Wilhelm-Stahl-Allee 2 18196 Dummerstorf Germany
                [3 ] Research Institute for the Biology of Farm Animals, Research Unit ‘Functional Genome Analysis’ Wilhelm-Stahl-Allee 2 18196 Dummerstorf Germany
                [4 ] Department of Genetics, University of Cordoba, Campus Rabanales, Building C-5 14071 Cordoba Spain
                [5 ] Royal Veterinary College, Department of Pathology and Infectious Diseases Hawkshead Lane North Mymms, Herts AL9 7TA United Kingdom
                Author notes
                Article
                v100012 10.1051/vetres/2010041
                10.1051/vetres/2010041
                2920636
                20615380
                500f015c-2121-42e1-b393-95e4ba123195
                © INRA, EDP Sciences, 2010
                History
                : 06 January 2010
                : 08 July 2010
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 35, Pages: 18
                Categories
                Original Article

                Veterinary medicine
                apicomplexan parasite,transcriptomic,host cell interaction,eimeria bovis,endothelial cell

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