TRYPANOSOMA CRUZI INFECTION INDUCES THE EXPRESSION OF WNT/FRIZZLED SIGNALING PATHWAY PROTEINS INVOLVED IN MODULATE THE INFLAMMATORY RESPONSE

VOLPINI, XIMENA; AMBROSIO, LF; ELIZALDE, C; MOTRAN, CLAUDIA CRISTINA

Mar del Plata

Congreso; LXII Reunión científica de la Sociedad Argentina de Inmunología y LIX REUNIÓN CIENTÍFICA ANUAL Sociedad Argentina de Investigación Clínica; 2014

SAI-SAIC

It has been postulated that Chagas disease, caused by T. cruzi, results from several factors such as parasite chronic persistence and progressive inflammatory destruction of target tissues. Tissue damage may be mediated by a direct effect of the parasite or/ and by a harmful immune response generated by the host. Therefore, is it clear that during infection with T. cruzi is essential to establish, with accurately kinetics at early stages an inflammat ory response (essential to the effective elimination of the parasites) followed by the activation of regulatory circuits capable to control the inflammation. Wnt/Frizzled signaling, essential for embryonic development, is induced in macrophages (Mo) by inflammatory stimulus and signal through canonical (β-catenin-dependent) and non-canonical (β-catenin-independent) pathways to amplify or control the inflammation. Our aim was to determine whether T. cruzi infection is able to modulate the expression of Wnt pathway?s members. For that, C57BL/6 mice (n=5) were infected with 3000 trypomastigotes (tp) of T.cruzi and the expression of Wnt 3a, Wnt5a and β-catenin was determined by Western blot at different times post-infection (pi) in spleen mononuclear cells. T. cruzi infection induced an up-regulation of Wnt5a and β-catenin at the peak of parasitemia (d 17 pi) compared with non-infected mice (n=5) (p< 0.05). Next, Wnt proteins induction in Mo, the known host cells of T. cruzi, was studied in bone marrow derived Mo from wt or TLR-4 KO mice infected in vitro with T. cruzi tp (cells:tp= 1:3) for 12 h. Wnt 3a, Wnt5a and β-catenin were significantly up-regulated in Mo by the infection. Interestingly, compared to wt cells, Wnt3a expression in TLR-4 deficient Mo was reduced while Wnt5a expression was increased in response to T. cruzi infection. The modulation of Wnt /Frizzled signaling during T. cruzi infection may allow the design of more effective strategies with the purpose of enhancing the protective response and the control of pathogen inflammation.