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Macrophage-parasite relationship in theileriosis. Reversible phenotypic and functional dedifferentiation of macrophages infected with Theileria annulata

1997; Oxford University Press; Volume: 61; Issue: 4 Linguagem: Inglês

10.1002/jlb.61.4.459

1938-3673

Heinz Sager, William C. Davis, D. Dobbelaere, Thomas W. Jungi,

Toxin Mechanisms and Immunotoxins

Abstract Theileria annulata is a tick-transmitted protozoan parasite of cattle, which transforms cells of macrophage (Mɸ) or B cell lineage. Bone marrow cells, bone marrow cell-derived, and monocyte-derived Mɸ were 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 down-regulated. Likewise, transformed cells failed to express Mɸ functions (Fc-receptor-mediated phagocytosis, phorbol myristate acetate-induced oxidative burst, lipopolysaccharide-induced tumor necrosis factor α, and nitric oxide generation and procoagulant activity up-regulation). Mɸ origin was assured by homogeneity of the starting population, cloning of cells by limiting dilution, and repeated microscopic and flow cytometric monitoring of the cell lines. Elimination of the parasite by treatment with BW720c resulted in the reacquisition of monocyte lineage properties, as evidenced by up-regulation of CD14, and by re-acquisition of the capacity to ingest opsonized sheep red blood cells and bacteria. Thus, Mɸ transformed by T. annulaia appear to undergo a process of parasite-induced dedifferentiation but reassume the differentiated phenotype upon elimination of the parasite.