Activation of transforming growth factor β by Trypanosoma cruzi

Abstract

The anti-inflammatory cytokine, transforming growth factor β (TGFβ), plays an important role in Chagas disease, which is caused by the protozoan parasite Trypanosoma cruzi. In the current study, we show that the addition of an anti-TGFβ antibody inhibited T. cruzi infection of cardiomyocytes, demonstrating the requirement for active endogenous TGFβ. As TGFβ is synthesized as a biologically inactive precursor, which is proteolytically processed to yield a mature, active homodimer, we hypothesized that T. cruzi could activate latent TGFβ. To test this, we added recombinant latent TGFβ to a TGFβ-responsive reporter cell line in the presence of T. cruzi. We observed that T. cruzi was able to activate latent recombinant TGFβ in this cellular model. We then investigated the ability of T. cruzi to activate latent TGFβ in vitro. We found that live T. cruzi, or cytosolic extracts of T. cruzi, activated latent TGFβ in a dose- and temperature-dependent manner. The agent involved in TGFβ activation was shown to be thermolabile and hydrophobic. Taken together, our studies demonstrate that T. cruzi directly activates latent TGFβ. This activation is required for parasite entry into the mammalian cells and is likely to play an important role in modulating the outcome of T. cruzi infection. © 2004 Blackwell Publishing Ltd.