CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Trypanosoma cruzi infection induces the expression of WNT/FRIZZLED signaling pathway proteins involved in modulate the inflamatory response
Autor/es:
VOLPINI XIMENA; AMBROSIO LAURA FERNANDA; ELIZALDE CARINA; MOTRAN CLAUDIA CRISTINA
Reunión:
Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología-SAI.; 2014
Resumen:
It has been postulated that Chagas disease, caused by T. cruzi,results from several factors such as parasite chronic persistenceand progressive inflammatory destruction of target tissues. Tissuedamage 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 toestablish, with accurately kinetics at early stages an inflammat oryresponse (essential to the effective elimination of the parasites)followed by the activation of regulatory circuits capable to controlthe inflammation. Wnt/Frizzled signaling, essential for embryonicdevelopment, is induced in macrophages (Mo) by inflammatorystimulus and signal through canonical (β-catenin-dependent) andnon-canonical (β-catenin-independent) pathways to amplify orcontrol the inflammation. Our aim was to determine whether T.cruzi infection is able to modulate the expression of Wnt pathway?smembers. For that, C57BL/6 mice (n=5) were infected with 3000trypomastigotes (tp) of T.cruzi and the expression of Wnt 3a,Wnt5a and β-catenin was determined by Western blot at differenttimes post-infection (pi) in spleen mononuclear cells. T. cruzi infectioninduced an up-regulation of Wnt5a and β-catenin at the peakof parasitemia (d 17 pi) compared with non-infected mice (n=5) (p<0.05). Next, Wnt proteins induction in Mo, the known host cells ofT. cruzi, was studied in bone marrow derived Mo from wt or TLR-4KO mice infected in vitro with T. cruzi tp (cells:tp= 1:3) for 12 h. Wnt3a, Wnt5a and β-catenin were significantly up-regulated in Mo bythe infection. Interestingly, compared to wt cells, Wnt3a expressionin TLR-4 deficient Mo was reduced while Wnt5a expression wasincreased in response to T. cruzi infection. The modulation of Wnt/Frizzled signaling during T. cruzi infection may allow the design ofmore effective strategies with the purpose of enhancing the protectiveresponse and the control of pathogen inflammation.