Trypanosoma cruzi trans-sialidase potentiates T cell activation through antigen-presenting cells: role of IL-6 and Bruton's tyrosine kinase

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Abstract
Polyclonal lymphocyte activation and hypergammaglobulinemia characterize the acute phase of Chagas' disease, a debilitating condition caused by Trypanosoma cruzi. Such pathogenic hyper‐reactivities not only compromise specific host defense against the pathogen, but may also contribute to infection‐induced chronic autoimmune responses. Recent studies showed that T. cruzitrans‐sialidase (TS) directly stimulates the polyclonal proliferation and Ig secretion of normal murine B cells in a T‐independent, Bruton′s tyrosine kinase (Btk)‐dependent manner. Relatedto this observation, we now show that parasite‐derived and recombinant TS potentiate the proliferation and cytokine secretion of normal T cells triggered by antigen‐specific and non‐specific stimuli. TS potentiates T cell activation through stimulating B cells and macrophages, independent of CD40/CD40L and CD43 pathways. In contrast, optimal TS potentiation requires interleukin‐6 (IL‐6) and Btk, as it is significantly reduced in splenocytes from IL‐6–/– and Btk‐defective Xid mice. The results suggest that TS, directly and indirectly, activates both antigen‐presenting cell and T cell compartments, and that TS‐induced IL‐6 may further amplify such activation. These observations open up the possibility that TS drives the polyclonal lymphocyte activation in acute T. cruzi infection, a phenomenon contributing to the pathogenesis of Chagas' disease.