Transforming Growth Factor α Binds to Trypanosoma cruzi Amastigotes To Induce Signaling and Cellular Proliferation

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Abstract
Macrophages secrete transforming growth factor α (TGF-α) to trigger proliferation of cancer cells. Here, we report a new role for TGF-α in modulating the direct cellular proliferation of a parasitic protozoan, Trypanosoma cruzi . Amastigotes present two classes of receptors for TGF-α with different binding affinities. 125 I-TGF-α binding was competed by an excess of cold epidermal growth factor and TGF-α but not by an irrelevant molecule. Upon binding of TGF-α to amastigotes, the ligand is internalized, inducing trypanosome tyrosine phosphorylation of 90- and 87-kDa proteins and increasing DNA synthesis and proliferation of amastigotes. Furthermore, exposure of macrophages to TGF-α induced increased amastigote proliferation. These results describe a novel mechanism used by amastigotes to regulate their proliferation mediated by a TGF-α-dependent signal transduction pathway.