Costimulation of host T lymphocytes by a trypanosomal trans-sialidase: involvement of CD43 signaling.
Trans-sialidase is a membrane-bound and shed sialidase from Trypanosoma cruzi, the protozoan parasite responsible for Chagas disease. We investigated the role of soluble trans-sialidase on host CD4+ T cell activation. Trans-sialidase activated naive CD4+ T cells in vivo. Both enzymatically active and inactive recombinant trans-sialidases costimulated CD4+ T cell activation in vitro. Costimulation resulted in increased mitogen-activated protein kinase activation, proliferation, and cytokine synthesis. Furthermore, active and inactive trans-sialidases blocked activation-induced cell death in CD4+ T cells from T. cruzi-infected mice. By flow cytometry, inactive trans-sialidase bound the highly sialylated surface Ag CD43 on host CD4+ T cells. Both costimulatory and antiapoptotic effects of trans-sialidases required CD43 signaling. These results suggest that trans-sialidase family proteins are involved in exacerbated host T lymphocyte responses observed in T. cruzi infection.
Todeschini
Adriane R
AR
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Fiocruz, Rio de Janeiro, RJ 21944-970, Brazil.
Nunes
Marise P
MP
Pires
Rachel S
RS
Lopes
Marcela F
MF
Previato
José O
JO
Mendonça-Previato
Lúcia
L
DosReis
George A
GA
D000818:Animals; D015703:Antigens, CD; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D006023:Glycoproteins; D007279:Injections, Subcutaneous; D007399:Interphase / Q000276:immunology; D051917:Leukosialin; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009439:Neuraminidase / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000276:immunology*
D015703:Antigens, CD; D006023:Glycoproteins; D051917:Leukosialin; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; C069715:trans-sialidase; D009439:Neuraminidase