Trypanosoma cruzi infection modulates in vivo expression of major histocompatibility complex class II molecules on antigen-presenting cells and T-cell stimulatory activity of dendritic cells in a strain-dependent manner.
A striking feature of Chagas' disease is the diversity of clinical presentations. Such variability may be due to the heterogeneity among Trypanosoma cruzi isolates or to the host immune response. Employing two strains which differ in their virulence, we investigated the effect of in vivo infection on professional antigen-presenting cells (APC). Acute infection with the virulent RA strain downregulated the expression of major histocompatibility complex (MHC) class II on splenic dendritic cells (DC) and inhibited its induction on peritoneal macrophages and splenic B cells. It also impaired the ability of DC to prime allogeneic T cells and to form homotypic clusters, suggesting a low maturation state of these cells. In contrast, the low-virulence K98 strain maintained the expression of MHC class II on DC or stimulated it on peritoneal macrophages and B cells and preserved DC's T-cell priming capacity and homotypic clustering. DC from RA-infected mice elicited a lower activation of T. cruzi-specific T-cell proliferation than those from K98-infected mice. APC from RA-infected mice that reached the chronic phase of infection restored MHC class II levels to those found in K98-infected mice and upregulated costimulatory molecules expression, suggesting that the immunosuppression caused by this strain is only transient. Taken together, the results indicate that in vivo infection with T. cruzi modulates APC functionality and that this is accomplished in a strain-dependent manner.
Alba Soto
Catalina D
CD
Department of Microbiology, Parasitology and Immunology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Mirkin
Gerardo A
GA
Solana
Maria E
ME
González Cappa
Stella M
SM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology
D000949:Histocompatibility Antigens Class II