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United States Department of Agriculture

Agricultural Research Service

Research Project: Pharmacological and Immunologic Interventions Against Vector-Borne Bovine and Equine Babesiosis

Location: Animal Diseases Research

Title: Lymphocytes and macrophages are infected by theileria equi, but T cells and B cells are not required to establish infection in vivo

Authors
item Ramsay, Joshua -
item Ueti, Massaro
item Johnson, W Carl
item Scoles, Glen
item Knowles, Donald
item Mealey, Robert -

Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 5, 2013
Publication Date: October 7, 2013
Citation: Ramsay, J.D., Ueti, M.W., Johnson, W.C., Scoles, G.A., Knowles Jr, D.P., Mealey, R.H. 2013. Lymphocytes and macrophages are infected by theileria equi, but T cells and B cells are not required to establish infection in vivo. PLoS One. DOI: 10.1371.

Interpretive Summary: Theileria equi has a biphasic life cycle in horses: 1) intraleukocyte development and 2) erythrocytic parasitemia. Unlike Theileria spp. that infect cattle, the intraleukocyte stage (schizont) of T. 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, T. 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. Peripheral blood mononuclear cells were infected in vitro and the phenotype of infected cells determined by flow cytometry and immunofluorescence microscopy. The results demonstrated that the host cell range of T. 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 were inoculated with T. equi sporozoites. SCID horses developed high parasitemia, confirming that macrophages were sufficient for in vivo infection. These data suggest that the factors mediating T. equi leukocyte invasion and intracytoplasmic differentiation are common to several leukocyte subsets and are less restricted than for T. annulata and T. parva.

Technical 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.

Last Modified: 12/22/2014
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