Effects of Exogenous Transforming Growth Factor β onTrypanosoma congolenseInfection in Mice

Abstract

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 antiinflammatory properties of transforming growth factor ␤1 (TGF-␤1) and its potential to enhance immunity against protozoan parasites, we examined the effects of intraperitoneally delivered TGF-␤1 in C57BL/6 mice infected with Trypanosoma congolense, the hemoprotozoan parasite causing nagana in cattle. A triple dose of 10 ng TGF-␤1 significantly reduced the first parasitemic peak and delayed mortality of infected mice. Furthermore, exogenous TGF-␤1 significantly decreased the development of trypanosome-induced anemia and splenomegaly. The apparent TGF-␤1-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-␤1-pretreated mice exhibited a significant reduction in the trypanosome-induced hyperexpansion of B cells. Furthermore, evidence is provided herein that exogenous TGF-␤1 activates macrophages that may contribute to parasite control. Collectively, these data indicate that exogenous TGF-␤1 is immunostimulative, inducing partial protection against T. congolense infection, possibly through mechanisms involving innate immune responses.

Differential Invasion of Trypanosoma brucei brucei and Lymphocytes into the Brain of C57BL/6 and 129Sv/Ev Mice

“…Although, to our knowledge, the role of TGF-b in T. brucei infection has not been investigated; previous studies have addressed the role of TGF-b in other trypanosome infections. Inoculation of exogenous TGF-b, significantly decreased the development of trypanosome-induced anaemia and splenomegaly, suggesting an anti-inflammatory role in a model of infection with T. congolense [33]. In agreement with these results, we found that TGF-b expression in the brain was higher in Sv-129 than in B6 animals.…”

Quantitative Differences in Immune Responses in Mouse Strains that Differ in their Susceptibility to Trypanosoma brucei brucei Infection

“…In contrast, B6B-F1 mice that exhibited relative trypanotolerance had significantly higher levels of VSGspecific plasma Abs. These observations support and further highlight the protective role of parasite-antigen-specific Abs during trypanosomosis [5,7,12]. Recent studies suggest that Abs of the IgG class, particularly IgG1 and IgG2a, are more closely correlated with trypanotolerance than IgM [2,7,9,19].…”

Interleukin‐12p70–Dependent Interferon‐γ Production Is Crucial for Resistance in African Trypanosomiasis

“…The role of IL-12 in T. b. brucei infection therefore seems to be limited to the more chronic stage of disease and the promotion of the TNF and IFN-g production necessary to control parasitemia. Natural killer cells, which are thought to be necessary for resistance during initial infection, are activated by both IL-12 and IL-18 [36], and IL-18 thus may effectively drive the Th1 response in the absence of IL-12. Furthermore, in a recent study, Drennan et al [37] found that MyD88 signaling is crucial for resistance and that there is a role for Toll-like receptor (TLR) 9 in this immune pathway.…”