Uptake of host cell transforming growth factor-beta by Trypanosoma cruzi amastigotes in cardiomyocytes: potential role in parasite cycle completion.
The cytokine transforming growth factor-beta (TGF-beta) 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-beta, we observed stronger immunoreactivity in parasites than in host cells. TGF-beta immunoreactivity evolved during parasite cycle progression, with intense staining in amastigotes versus very faint staining in trypomastigotes. TGF-beta was present on the surface of amastigotes, in the flagellar pocket, and in intraparasitic vesicles as revealed by electron microscopy. However, no ortholog TGF-beta 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-beta was most probably taken up by the parasite from the host cell cytoplasm because such an internalization process of biotinylated TGF-beta 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-beta to control its own intracellular life cycle.
Waghabi
Mariana C
MC
Laboratorios de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
Keramidas
Michelle
M
Bailly
Sabine
S
Degrave
Wim
W
Mendonça-Lima
Leila
L
Soeiro
Maria de Nazaré C
Mde N
Meirelles
Maria de Nazareth L
Mde N
Paciornik
Sidnei
S
Araújo-Jorge
Tania C
TC
Feige
Jean-Jacques
JJ
D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000378:metabolism; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D016650:Fluorescein-5-isothiocyanate; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D007211:Indoles; D008018:Life Cycle Stages; D051379:Mice; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000469:parasitology; D010590:Phalloidine / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D012235:Rhodamines; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000254:growth & development* / Q000469:parasitology* / Q000648:ultrastructure
D000199:Actins; D005456:Fluorescent Dyes; D007211:Indoles; D011994:Recombinant Proteins; D012235:Rhodamines; D016212:Transforming Growth Factor beta; D010590:Phalloidine; C007293:DAPI; D016650:Fluorescein-5-isothiocyanate