Trypanosoma cruzi surface mucin TcMuc-e2 expressed on higher eukaryotic cells induces human T cell anergy, which is reversible.
Chagas' disease is a chronic, debilitating, multisystemic disorder that affects millions of people in Latin America. The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas' disease, has a large number of O-glycosylated Thr/Ser/Pro-rich mucin molecules on its surface (TcMuc). These mucins are the main acceptors of sialic acid and have been suggested to play a role on various host-parasite interactions, such as adhesion to macrophages, protection from complement lysis, and immunomodulation of the immune response mounted by the host. To observe the immunologic effect obtained by the heterologous expression of a TcMuc gene in higher eukaryotic cells exposed to xenogeneic lymphocytes, we developed a strategy based on the transfection of a known T. cruzi mucin gene (TcMuc-e2) into Vero cells. In contrast to the brisk proliferation and activation of human lymphocytes observed at 3, 4, and 5 days induced by normal Vero cells, neither proliferation nor significant activation of human lymphocytes was observed with TcMuc-e2-transfected Vero cells. This TcMuc-e2 mucin-induced suppression of T cell response can be reversed by the addition of exogenous IL-2. In addition it was demonstrated that the immunosuppressive reaction was not related to the induction of an important degree of apoptosis in human lymphocytes. Posttranslational modification are required for the inhibitory effect that TcMuc-e2 exerts when transfected to Vero cells. O-glycosylation and sialylation are required to obtain the immunomodulatory effect as assessed by O-sialoglycoprotease and neuraminidase treatments. These results are consistent with other studies showing that surface glycoconjugates from T. cruzi and mammalian cells can induce an inhibition of the immune response.
Argibay
Pablo F
PF
Instituto de Ciencias Básicas y Medicina Experimental, Hospital Italiano de Buenos Aires, Gascón 450, (1181) Buenos Aires, Argentina.
Di Noia
Javier M
JM
Hidalgo
Alejandra
A
Mocetti
Esteban
E
Barbich
Mariana
M
Lorenti
Alicia S
AS
Bustos
Daniel
D
Tambutti
Monica
M
Hyon
Sung H
SH
Frasch
Alberto C C
AC
Sánchez
Daniel O
DO
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002522:Chlorocebus aethiops; D017635:Clonal Anergy / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D008213:Lymphocyte Activation; D009077:Mucins / Q000378:metabolism* / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology; D014349:Trypanosoma cruzi / Q000378:metabolism*; D014709:Vero Cells
D009077:Mucins