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(American Journal of Pathology. 2005;167:993-1003.)
© 2005 American Society for Investigative Pathology

Uptake of Host Cell Transforming Growth Factor-ß by Trypanosoma cruzi Amastigotes in Cardiomyocytes

Potential Role in Parasite Cycle Completion

Mariana C. Waghabi*, Michelle Keramidas{dagger}, Sabine Bailly{dagger}, Wim Degrave{ddagger}, Leila Mendonça-Lima{ddagger}, Maria de Nazaré C. Soeiro*, Maria de Nazareth L. Meirelles, Sidnei Paciornik§, Tania C. Araújo-Jorge* and Jean-Jacques Feige{dagger}

From the Laboratorios de Biologia Celular* and Ultraestrutura Celular, Departamento de Ultra-estrutura e Biologia Celular and Laboratorio de Genomica Funcionale Bioinformatica, Departamento de Bioquímica e Biologia Molecular,{ddagger} Instituto Oswaldo Cruz, Rio de Janeiro, Brazil; the Laboratorio de Processamento Digital de Imagens,§ Pontifica Universidade Catolica, Rio de Janeiro, Brazil; and the Institut National de la Santé et de la Recherche Médicale Equipe Mixte 01-05, Département Réponse et Dynamique Cellulaire,{dagger} Commissariat à l’Énergie Atomique, Grenoble, France

The cytokine transforming growth factor-ß (TGF-ß) plays various functions in the control of Trypanosoma cruzi infectivity and in the progression of Chagas’ disease. When we immunostained T. cruzi-infected cardiomyocytes (after either in vivo or in vitro infections) for TGF-ß, we observed stronger immunoreactivity in parasites than in host cells. TGF-ß immunoreactivity evolved during parasite cycle progression, with intense staining in amastigotes versus very faint staining in trypomastigotes. TGF-ß was present on the surface of amastigotes, in the flagellar pocket, and in intraparasitic vesicles as revealed by electron microscopy. However, no ortholog TGF-ß gene could be identified in the genome of T. cruzi by in silico analysis or by extensive polymerase chain reaction and reverse transcriptase-polymerase chain reaction studies. Immunoreactive TGF-ß was most probably taken up by the parasite from the host cell cytoplasm because such an internalization process of biotinylated TGF-ß could be observed in axenic amastigotes in vitro. These observations represent the first example of a novel mechanism by which a primitive unicellular protozoan can use host cell TGF-ß to control its own intracellular life cycle.




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M. C. Waghabi, M. Keramidas, C. M. Calvet, M. Meuser, M. d. N. C. Soeiro, L. Mendonca-Lima, T. C. Araujo-Jorge, J.-J. Feige, and S. Bailly
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