Abstract
Theileria equi has a biphasic life cycle in horses, with a period of intraleukocyte development followed by patent erythrocytic parasitemia that causes acute and sometimes fatal hemolytic disease. Unlike Theileria spp. that infect cattle (Theileria parva and Theileria annulata), the intraleukocyte stage (schizont) of Theileria equi does not cause uncontrolled host cell proliferation or other significant pathology. Nevertheless, schizont-infected leukocytes are of interest because of their potential to alter host cell function and because immune responses directed against this stage could halt infection and prevent disease. Based on cellular morphology, Theileria equi has been reported to infect lymphocytes in vivo and in vitro, but the specific phenotype of schizont-infected cells has yet to be defined. To resolve this knowledge gap in Theileria equi pathogenesis, peripheral blood mononuclear cells were infected in vitro and the phenotype of infected cells determined using flow cytometry and immunofluorescence microscopy. These experiments demonstrated that the host cell range of Theileria equi was broader than initially reported and included B lymphocytes, T lymphocytes and monocyte/macrophages. To determine if B and T lymphocytes were required to establish infection in vivo, horses affected with severe combined immunodeficiency (SCID), which lack functional B and T lymphocytes, were inoculated with Theileria equi sporozoites. SCID horses developed patent erythrocytic parasitemia, indicating that B and T lymphocytes are not necessary to complete the Theileria equi life cycle in vivo. These findings suggest that the factors mediating Theileria equi leukocyte invasion and intracytoplasmic differentiation are common to several leukocyte subsets and are less restricted than for Theileria annulata and Theileria parva. These data will greatly facilitate future investigation into the relationships between Theileria equi leukocyte tropism and pathogenesis, breed susceptibility, and strain virulence.
Highlights
Theileria equi is a tick-transmitted apicomplexan hemoprotozoan parasite that causes acute hemolytic disease and persistent infection of wild and domestic equids throughout the world [1,2]
In the sporozoite inoculated group, parasitemia was detectable by real time PCR 9–15 days post inoculation (DPI), with peak parasitemia of 106–107 parasites/ml whole blood occurring 12–19 DPI (Fig. 1A)
The subtle differences between lymphocyte and monocyte/macrophage morphology are, distorted by intracytoplasmic schizont development and precludes determining the specific identity of infected cells
Summary
Theileria equi is a tick-transmitted apicomplexan hemoprotozoan parasite that causes acute hemolytic disease (equine piroplasmosis) and persistent infection of wild and domestic equids throughout the world [1,2]. The life cycle of Theileria equi is biphasic in the mammalian host, with a period of intraleukocyte development (pre-erythrocytic schizogony) followed by patent erythrocytic parasitemia [3,4]. The pre-erythrocytic stage of T. equi has not been associated with clinical disease in equids and relatively little work has been done to characterize host-parasite interaction during this phase of infection. In vitro and in vivo, tick-transmitted T. equi sporozoites infect mononuclear leukocytes and differentiate into multinucleated schizonts (schizogony), which further divide to form erythroinvasive merozoites [4].
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