Cruzipain, a major Trypanosoma cruzi cystein protease in the host-parasite interplay

SUSANA GEA; NATALIA GUIÑAZÚ; ANDREA PELLEGRINI; EUGENIO ANTONIO CARRERA-SILVA; LAURA GIORDANENGO; ROXANA CANO; MARÍA DEL PILAR AOKI

Inmunología

Lugar: Madrid, España; Año: 2006 vol. 25 p. 225 - 238

0213-9626

The protozoan parasite Trypanosoma cruzi, etiological agent of Chagas disease, is endemic in Central and South America and produce the most common myocarditis worldwide. Parasite persistence eventually leads to a debilitating heart disease that kills more than 50,000 people every year. There is no consensus as to whether tissue damage is caused entirely by the parasite or is exacerbated by an autoimmune response. In both models of disease progression, cruzipain- the major cysteine proteinase of T. cruzi- has been suggested to play an important role. Cruzipain is a member of the papain superfamily, and it is expressed as a complex mixture of isoforms by different strains of the parasite, as well as, by all its developmental stages. This parasite glycoprotein plays a role in the process of T. cruzi internalization into mammalian cells, as proved by specific enzyme inhibitors which interfere with cell invasion and also inhibit parasite replication. In addition, cruzipain not only is essential for parasite survival but also generates a strong immune response in infected individuals, these characteristics signal cruzipain as a potential target for drug therapy and for the generation of immune response. This review analyses our present knowledge of cruzipain role in the disease pathogenesis, its involvement in host cell invasion, immune activation and evasion by T. cruzi in experimental models and humans infections. Ongoing studies in this research area may provide novel therapeutic strategies that could enhance the immunoprotective response while preventing the deleterious parasite elicited responses observed during Chagas disease.