Effects of exogenous transforming growth factor beta on Trypanosoma congolense infection in mice.
The socioeconomic implications of trypanosomosis in sub-Saharan Africa and the limitations of its current control regimes have stimulated research into alternative control methods. Considering the pro- and anti-inflammatory properties of transforming growth factor beta1 (TGF-beta1) and its potential to enhance immunity against protozoan parasites, we examined the effects of intraperitoneally delivered TGF-beta1 in C57BL/6 mice infected with Trypanosoma congolense, the hemoprotozoan parasite causing nagana in cattle. A triple dose of 10 ng TGF-beta1 significantly reduced the first parasitemic peak and delayed mortality of infected mice. Furthermore, exogenous TGF-beta1 significantly decreased the development of trypanosome-induced anemia and splenomegaly. The apparent TGF-beta1-induced antitrypanosome protection, occurring mainly during the early stage of infection, correlated with an enhanced parasite antigen-specific Th1 cell response characterized by a skewed type I cytokine response and a concomitant stronger antitrypanosome immunoglobulin G2a antibody response. Infected TGF-beta1-pretreated mice exhibited a significant reduction in the trypanosome-induced hyperexpansion of B cells. Furthermore, evidence is provided herein that exogenous TGF-beta1 activates macrophages that may contribute to parasite control. Collectively, these data indicate that exogenous TGF-beta1 is immunostimulative, inducing partial protection against T. congolense infection, possibly through mechanisms involving innate immune responses.
Namangala
Boniface
B
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
Sugimoto
Chihiro
C
Inoue
Noboru
N
D000740:Anemia; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000008:administration & dosage*; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia; D013163:Splenomegaly; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000276:immunology* / Q000494:pharmacology; D014348:Trypanosoma congolense / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000150:complications / Q000276:immunology*
D000913:Antibodies, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D016212:Transforming Growth Factor beta