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Infection and Immunity, July 2003, p. 4201-4205, Vol. 71, No. 7
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.7.4201-4205.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Binds to Trypanosoma cruzi Amastigotes To Induce Signaling and Cellular Proliferation
Fernando Villalta, and Maria F. Lima*
Department of Microbiology, Meharry Medical College, Nashville, Tennessee 37208
Received 27 November 2002/ Returned for modification 1 April 2003/ Accepted 14 April 2003
Macrophages secrete transforming growth factor
(TGF-
) to trigger proliferation of cancer cells. Here, we report a new role for TGF-
in modulating the direct cellular proliferation of a parasitic protozoan, Trypanosoma cruzi. Amastigotes present two classes of receptors for TGF-
with different binding affinities. 125I-TGF-
binding was competed by an excess of cold epidermal growth factor and TGF-
but not by an irrelevant molecule. Upon binding of TGF-
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-
induced increased amastigote proliferation. These results describe a novel mechanism used by amastigotes to regulate their proliferation mediated by a TGF-
-dependent signal transduction pathway.
Present address: Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, Chapel Hill, NC 27514.
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