The antioxidant enzyme network of Trypanosoma cruzi: an emerging virulence factor?

PIACENZA, L; ZAGO, M.P; PELUFFO, G; ALVAREZ, MN; KELLY, M.K; WILKINSON, S.R.; BASOMBRIO, M.A; RADI, R

Águas de Lindóia-Sao Paulo, Brasil

Congreso; XXIV Meeting of the Brazilian Society of Protozoology XXXV Annual Meeting on Basic Research in Chagas Disease; 2008

Sociedad Brasilera de Protozoología

Virulence of Trypanosoma cruzi strains towards the host depends on different genetic and biochemical factors known to participate in the severity of Chagas disease. The suggested increased expression of molecules of the antioxidant network including trypanothione synthase (TcTS), tryparedoxin, tryparedoxin peroxidases, and iron-containing superoxide dismutases during metacyclogenesis, constitutes a remarkable event that allows to hypothesize that parasites are preconditioned in an effort to overcome the challenge raised by macrophage-derived reactive oxygen and nitrogen species upon infection. In this line, and using several isolates (10 strains) that belongs to the major phylogenetic lineages TCI and TCII, we investigated for an association between virulence (ranging from highly aggressive to extremely attenuated isolates at the parasitemia and histopathology level) and the antioxidant enzyme content. Antibodies rised against TcTS, ascorbate peroxidase (TcAPX), mitochondrial and cytosolic tryparedoxin peroxidases (TcMPX, TcCPX) and trypanothione reductase (TcTR) were used to evaluate the antioxidant enzyme levels in epimastigotes and metacyclic trypomastigotes of the different T. cruzi strains. A direct correlation was found between levels of TcTS, TcMPX and TcCPX with the parasitemia elicited by the different isolates studied (r=0.908, 0.953, 0.738 respectively, P<0.05). The strongest association was found with the TcTS which was not only increased on the more virulent strains but also rised during the differentiation to the infective form, whereas TcAPX showed the weakest correlation. Moreover, independently of its virulence, levels of antioxidant enzymes were higher in the trypomastigote stage. At the cellular level, this was accompanied by an elevated resistance of highly virulent T. cruzi populations to H2O2 and peroxynitrite challenge. Finally, T. cruzi transformed for the overexpression of TcCPX were more infective in macrophages activated for the production of peroxynitrite suggesting that the parasite antioxidant armamentarium at the onset of infection represents a new virulence factor involved in the establishment of the disease.