MACROPHAGE-PARASITE RELATIONSHIP IN THEILERIOSIS - REVERSIBLE PHENOTYPIC AND FUNCTIONAL DEDIFFERENTIATION OF MACROPHAGES INFECTED WITH THEILERIA-ANNULATA

Theileria annulata is a tick-transmitted protozoan parasite of cattle, which transforms calls of macrophage (M phi) or B cell lineage. Bone marrow cells, bone marrow cell-derived, and monocyte-derived M phi wer e infected with T. annulata sporozoites, and the resulting cell lines were assessed for surface marker expression and function. Transformed Lines expressed histocompatibility complex (MHC) class-I and II, CD44, CD45, and the myeloid marker DH598-surface markers CD14, CD11b, M-M7, TH57A, and to a lesser extent CD11a/CD18, CD11c, and ACT(B), were dow nregulated, Likewise, transformed cells failed to express M phi functi ons (Fc-receptor-mediated phagocytosis, phorbol myristate acetate-indu ced oxidative burst, lipopolysaccharide-induced tumor necrosis factor alpha, and nitric oxide generation and procoagulant activity up-regula tion), M phi origin was assured by homogeneity of the starting populat ion, cloning of cells by limiting dilution, and repeated microscopic a nd flow cytometric monitoring of the cell lines. Elimination of the pa rasite by treatment with BW720c resulted in the reacquisition of monoc yte lineage properties, as evidenced by up-regulation of CD14, and by re-acquisition of the capacity to ingest opsonized sheep red blood cel ls and bacteria. Thus, M phi transformed by T. annulata appear to unde rgo a process of parasite-induced dedifferentiation but reassume the d ifferentiated phenotype upon elimination of the parasite.