IMBALANCE TOWARDS A TH2 PROFILE IS CAUSED BY TRYPANOSOMA CRUZI TRANS-SIALIDASE IN ACUTE STAGE OF CHAGAS DISEASE

RUIZ DÍAZ P; MUCCI J; CAMPETELLA O

Caxambú

Congreso; XXXI Annual Meeting of the Brazilian Society of Protozoology XLII Annual Meeting on Basic Research in Chagas' Disease; 2015

SBPZ - Sociedade Brasileira de Protozoologia

HP159 - IMBALANCE TOWARDS A TH2 PROFILE IS CAUSED BY TRYPANOSOMA CRUZI TRANS-SIALIDASE IN ACUTE STAGE OF CHAGAS DISEASERUIZ DIAZ, P.*1; MUCCI, J.1; CAMPETELLA, O.11.IIB-UNSAM, San Martin, ARGENTINA.e-mail:pruizdiaz@iibintech.com.arThe protozoan parasite Trypanosoma cruzi needs to acquire sialic acid to invade mammalian cells. For this, the parasite expresses the trans-Sialidase (TS), an enzyme able to transfer sialyl residues from host glycoproteins to its own mucins. Interestingly, two TS isoforms are known in T. cruzi, the enzymatically active (TS) isoform and the catalytically inactive (iTS) isoform, which has a mutation in the catalytic tyrosine but retains the ability to bind the substrate sugars. Previously we demonstrated that TS induces thymocyte depletion, thrombocytopenia, and absence of germinal centers in secondary lymphoid organs. This phenomena that can be prevented by the passive transfer of TS neutralizing antibody (13G9 mAb) to the infected mice. The resolution of the T. cruzi infection is dependent on the Th1 response, however both Th1 and Th2 clones are elicited during the infection. Due to the ability of TS to manipulate the immune system, we decided to explore their effect on T helper responses. We found that both TS and TSi decreased the IFN-gamma secretion while increasing the IL4 secretion in mouse- derived DO11.10 splenocytes stimulated with OVA323-339. Furthermore, in DO11.10 splenocytes transferred to OVA-immunized Balb/c mice both TS and TSi decreased the IL2 and IFN-gamma secretion with a concomitant increase of IL4. Similarly when we tested this model during T. cruzi infection we observed a significant amount of IFN-gamma but also a high level of IL4 and low of IL2. Interestingly, we could observe that the increase of IL4 and decrease of IL2 was prevented by passive transfer of 13G9 mAb. Finally, using neutralizing antibodies and transgenic mouse models we found that the antigen-presenting cell through IL10 regulates these phenomena. These results strongly support the idea that TS and TSi modulate Th1 differentiation and promote a non-protective Th2 response in the acute stage of Chagas? disease. Supported by:NIH, CONICET, ANPCyT Keywords:Trypanosoma cruzi; trans-sialidase; t helper