title: Trypanosoma cruzi trans-sialidase potentiates T cell activation through antigen-presenting cells: role of IL-6 and Bruton's tyrosine kinase.
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. cruzi trans-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. Related to 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.
authors.affiliation: Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, Boston 02111, USA.
authors.forename: W
authors.initials: W
authors.lastname: Gao
authors.forename: M A
authors.initials: MA
authors.lastname: Pereira
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology; D018920:Coculture Techniques; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D017353:Gene Deletion; D006023:Glycoproteins / Q000378:metabolism*; D007156:Immunologic Memory / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D051917:Leukosialin; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009439:Neuraminidase / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000201:enzymology*
chemical_list: D000941:Antigens; D015703:Antigens, CD; D016207:Cytokines; D006023:Glycoproteins; D015850:Interleukin-6; D051917:Leukosialin; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D003208:Concanavalin A; D023201:CD40 Ligand; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; C069715:trans-sialidase; D009439:Neuraminidase