Chagas disease affects over 18 million people in Latin America. The agent responsible is a protozoan parasite, Trypanosoma cruzi, transmitted by haematophagous insects. For survival in the hosts organism, it uses several strategies, but especially one of inhibiting the hosts immune response. Research scientists from the IRD and INSERM (1) who are studying this trypanosome found that one of the proteins it secretes, Tc52, is a virulence factor that plays a pivotal role in the infection mechanism. Combining different in–vitro and in-vivo approaches, they brought into evidence its role in the development of infection and performed the molecular characterization by peptide analysis of the minimal sequence of Tc52 that carries immunosuppressive activity. Knowledge of the biological activity of this factor raises the prospects for developing vaccination strategies or drugs to combat T. cruzi.
Chagas disease – or American trypanosomiasis – is a parasitic illness which affects nearly 20 million people mainly in tropical regions of Central and South America. The aetiological agent that causes it is a flagellate protozoan, Trypanosoma cruzi, transmitted to humans by haematophagous insects (Reduviidae). Research scientists from the IRD research unit "Pathogénie des Trypanosomatidae" and co-workers from INSERM have studied the parasites development cycle, its virulence and its involvement in the infection process, with a view to identifying possible prevention and control methods. Using techniques of cellular and molecular biology, and of biochemistry, they sought to identify the nature and function of T. cruzi genes which code for the factors responsible for the virulence, in particular a protein called Tc52.
As in any parasitic disease, the pathogens ability to survive in its vertebrate host depends on many mechanisms, especially one which weakens the hosts immune response. In Chagas disease, during its life-cycle in humans T. cruzi takes on two forms, an infective flagellate one (trypomastigote) which circulates and reproduces in the blood and another intracellular one without flagellum (amastigote), which in its turn multiplies to produce another batch of circulating forms. These two forms prove to be able to secrete this protein Tc52. The research team revealed it to have several activities, including enzyme activity (2) and an immunosuppressive activity. The protein released by T. cruzi influences in a complex way the physiology of the host cell. It acts on cells of the immune system, the macrophages and the dendritic cells, and notably blocks the production of interleukin 2 (IL-2), a cytokine necessary for T-lymphocyte proliferation, in this way exerting an immunosuppressive activity.
Bénédicte Robert | EurekAlert!
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