The Trypanosoma cruzi trans-sialidase is a T cell-independent B cell mitogen and an inducer of non-specific Ig secretion.
Polyclonal lymphocyte activation and hypergammaglobulinemia characterize the acute phase of many parasitic diseases, including Chagas' disease, a debilitating condition caused by Trypanosoma cruzi. Polyclonal lymphocyte activation correlates with disease susceptibility inT. cruzi infection. Thus, identifying factors that drive such reactivities should provide insight into mechanisms of parasite evasion from host immunity and of disease pathogenesis. Sensitization of mice with small doses of T. cruzi trans-sialidase (TS) turns the mice into highly susceptible hosts to T. cruzi. In addition, TS heterologously expressed in Leishmania major greatly enhances virulence of the parasite to mice. In attempt to study the mechanism of TS-induced virulence, we found that TS and its C-terminal long tandem repeat (LTR) are T-independent polyclonal activators for mouse B cells. While B cells deficient/defective in L-6, CD40 or Toll-like receptor-4 are similarly activated by TS as compared to wild-type cells, B cells from Bruton's tyrosine kinase-defective X-linked immunodeficient mice are remarkably insensitive to TS activation. TS-induced B cell activation in vitro is accompanied by Ig secretion independent of T cells. Furthermore, administration of TS into normal mice leads to non-specific Ig secretion that peaks 4-6 days after injection. Thus TS, through its LTR, induces abnormal polyclonal B cell activation and Ig secretion, which could explain in part its virulence-enhancing activity.
Gao
Wenda
W
Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Wortis
Henry H
HH
Pereira
Miercio A
MA
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001854:Bone Marrow Cells / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000494:pharmacology*; D007136:Immunoglobulins / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008934:Mitogens / Q000494:pharmacology*; D009439:Neuraminidase / Q000737:chemistry / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D020079:Terminal Repeat Sequences; D013936:Thymidine / Q000378:metabolism
D019013:CD40 Antigens; D016207:Cytokines; D006023:Glycoproteins; D007136:Immunoglobulins; D015850:Interleukin-6; D008934:Mitogens; C069715:trans-sialidase; D009439:Neuraminidase; D013936:Thymidine