THE TRANS-SIALIDASE FROM TRYPANOSOMA CRUZI REDUCES IL-2 AND IL-2RALPHA EXPRESSION ON T CELLS AND, VIA IL-10, PREVENTS TH1 RESPONSE ELICITATION

RUIZ DIAZ, P.; MUCCI, J.; MEIRA, A M; BOGLIOTTI, Y.; MUSIKANT D; LEGUIZAMON, MS; CAMPETELLA, O.

Los Cocos

Congreso; LXI Reunion Anual de la Sociedad Argentina de Inmunologia; 2013

Sociedad Argentina de Inmunologia

Trypanosoma cruzi, the agent of the American trypanosomiasis or Chagas disease, bypasses its lack of de novo synthesis of sialic acids by expressing a surface-anchored trans-sialidase (TS). This enzyme is a virulence factor involved in cell invasion and in several immune abnormalities. Since these effects exerted by the TS, we evaluated its effect on naïve CD4 T cells. TS mimicked the downregulation of IL-2 production and IL-2Rα expression induced by trypomastigotes on T cells, an infection hallmark. The effect of TS on CD4 T cell physiology was then assayed in a mouse model. Proliferation of naïve T cells to Ag-specific signaling was reduced by both isoforms of TS, either enzymatically active (aTS) or its lectin-like isoform (iTS), in in vivo and in vitro assays. The addition of TSs, strongly reduced TCR signaling as assayed by ZAP70 phosphorylation and consistently unbalanced the CD4 T cell Ag-specific response to the unprotective Th2 phenotype. These findings were reproduced even when strong culture conditions to induce Th1 were simultaneously applied, then supporting the TSs ability to deviate the response to the Th2 phenotype. Moreover, when Th1 cells were specifically stimulated in the presence of TSs, secretion of IL-2 and IFN-γ was strongly downregulated, while Th2 cells increased their IL-2 production. TSs induced IL-10 in Ag-presenting cells supporting this as the mechanisminvolved. Therefore, TS affected T cells all along the maturation stages from the induction of thymocyte apoptosis to deviation of primary response to Th2 phenotype and modulation of Th1 effector properties while stimulating the unprotective Th2 immune response. Therefore by taking control of the host immunoregulatory pathways, the TSs hamper the immune system from eliciting a protective response.