TcI Isolates of Trypanosoma cruzi Exploit the Antioxidant Network for Enhanced Intracellular Survival in Macrophages and Virulence in Mice

HOSAKOTE, Y.M. ; PIÑEYRO, M.D.; ROBELLO, C.; ZAGO, M.P.; DHIMAN, M.; BASOMBRÍO, M.A.; KOO, S.J.; PARODI­ TALICE, A.; GARG, N.J.

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2016 vol. 84 p. 1842 - 1856

0019-9567

Trypanosoma cruzi species is categorized into six discrete typing units (TcI to TcVI) of which TcI is most abundantly noted inthe sylvatic transmission cycle and considered the major cause of human disease. In our study, the TcI strains Colombiana(COL), SylvioX10/4 (SYL), and a cultured clone (TCC) exhibited different biological behavior in a murine model, ranging fromhigh parasitemia and symptomatic cardiomyopathy (SYL), mild parasitemia and high tissue tropism (COL), to no pathogenicity(TCC). Proteomic profiling of the insect (epimastigote) and infective (trypomastigote) forms by two-dimensional gel electrophoresis/matrix-assistedlaser desorption ionization?time of flight mass spectrometry, followed by functional annotation of the differentialproteome data sets (>2-fold change, P < 0.05), showed that several proteins involved in (i) cytoskeletal assembly andremodeling, essential for flagellar wave frequency and amplitude and forward motility of the parasite, and (ii) the parasite-specificantioxidant network were enhanced in COL and SYL (versus TCC) trypomastigotes. Western blotting confirmed the enhancedprotein levels of cytosolic and mitochondrial tryparedoxin peroxidases and their substrate (tryparedoxin) and iron superoxidedismutase in COL and SYL (versus TCC) trypomastigotes. Further, COL and SYL (but not TCC) were resistant toexogenous treatment with stable oxidants (H2O2 and peroxynitrite [ONOO]) and dampened the intracellular superoxide andnitric oxide response in macrophages, and thus these isolates escaped from macrophages. Our findings suggest that protein expressionconducive to increase in motility and control of macrophage-derived free radicals provides survival and persistencebenefits to TcI isolates of T. cruzi.