Abstract
Author SummaryAs part of their survival tactics, intracellular parasites often resort to cunning mechanisms to manipulate the cells they inhabit. Theileria, an important and particularly artful parasite of cattle in the tropics, transforms parasitized cells (that is, it induces continuous proliferation and protection from apoptosis—a state reminiscent of tumor cells). As a large, strictly intracellular syncytium, the transforming Theileria schizont cannot exit from the infected cell to invade other target cells. How then does the parasite ensure that each daughter cell, generated upon host cell division, remains infected and transformed? Our data show that the parasite co-opts the mitotic apparatus of the host cell and Plk1, a host protein kinase with a central regulatory role in mitosis and cytokinesis. As the host cell enters mitosis, the schizont binds to the microtubules that emanate symmetrically from the two spindle poles. This microtubule binding positions the schizont so that it spans the equatorial region of the mitotic cell where host cell chromosomes assemble. Then, as sister chromatids start to separate, the schizont associates with Plk1 and the central spindle that assembles between the separating chromosomes, with the activity of Plk1 presumably coordinating progression through mitosis with proper schizont positioning. This alignment with the central spindle positions the schizont to be included in the plane of cell division at the onset of cytokinesis, thus ensuring faithful passage of a Theileria schizont on to each daughter cell.
Highlights
The apicomplexan parasites Theileria annulata and T. parva are transmitted by ticks and cause severe lymphoproliferative disease in cattle in large areas of Africa, the Middle East, and Asia
We show that the parasite establishes a close interaction with both structures and found that its association with the central spindle depends on catalytically active Polo-like kinase 1 (Plk1)
TaC12 cells are of macrophage origin and in order to allow a morphological comparison, different stages of mitosis/cytokinesis as observed in a bovine control cell line of macrophage origin (BoMac) or cells that no longer contain the parasite are presented in Figure S1B and C
Summary
The apicomplexan parasites Theileria annulata and T. parva are transmitted by ticks and cause severe lymphoproliferative disease in cattle in large areas of Africa, the Middle East, and Asia. The pronounced pathology and high mortality are linked to the ability of Theileria to stimulate the uncontrolled proliferation of the cells it infects, inducing a phenotype typical of tumor cells. T. parva infects predominantly T- and B-lymphocytes, whereas T. annulata targets B-lymphocytes and macrophages/monocytes. Theileria-transformed cells proliferate independently of antigenic stimulation or exogenous growth factors. Parasitized cells become resistant to apoptosis [1,2,3] and acquire the capacity to invade and multiply in non-lymphoid as well as lymphoid tissues (reviewed in [4,5,6]). The natural host of Theileria, and in domestic animals that survive infection, the parasite persists for years, resulting in a carrier state
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