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Trypanosoma cruzi-induced host immune system dysfunction: A rationale for parasite immunosuppressive factor(s) encoding gene targeting

Abstract:

An intense suppression of T cell proliferation to mitogens and toantigens is observed in a large number of parasitic infections.The impairment of T cell proliferation also occurred during theacute phase of Chagas' disease, caused by the intracellularprotozoan parasite Trypanosoma cruzi. A wealth ofevidence has accumulated that illustrates the ability ofT. cruzi released molecules to influence directly avariety of diverse immunological functions. In this paper, wereview the data concerning the immunoregulatory effects ofT. cruzi Tc24 (a B cell activator antigen) and Tc52 (animmunosuppressive protein) released molecules on the host immunesystem. The gene targeting approach developed to further explorethe biological function(s) of Tc52 molecule, revealed interestingunexpected functional properties. Indeed, in addition to itsimmunusuppressive activity a direct or indirect involvement ofTc52 gene product alone or in combination with othercellular components in T. cruzi differentiation controlmechanisms have been evidenced. Moreover, targeted Tc52replacement allowed the obtention of parasite mutants exhibitinglow virulence in vitro and in vivo. Thus, thegeneration of a complete deficiency state of virulence factors bygene targeting should provide a means to assess the importance ofthese factors in the pathophysiological processes and diseaseprogression. It is hoped that such approaches might allowrational design of tools to control T. cruziinfections. © 2001 Hindawi Publishing Corporation.