Namangala Boniface, Sugimoto Chihiro, Inoue Noboru
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
Infect Immun. 2007 Apr;75(4):1878-85. doi: 10.1128/IAI.01452-06. Epub 2007 Jan 29.
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.
非洲撒哈拉以南地区锥虫病的社会经济影响及其当前防控措施的局限性,激发了人们对替代防控方法的研究。鉴于转化生长因子β1(TGF-β1)的促炎和抗炎特性及其增强针对原生动物寄生虫免疫力的潜力,我们研究了腹腔注射TGF-β1对感染刚果锥虫的C57BL/6小鼠的影响,刚果锥虫是一种导致牛患那加那病的血液原生动物寄生虫。三次注射10 ng TGF-β1可显著降低感染小鼠的首个寄生虫血症高峰并延迟其死亡。此外,外源性TGF-β1显著减少了锥虫诱导的贫血和脾肿大的发展。明显由TGF-β1诱导的抗锥虫保护作用主要发生在感染早期,这与以I型细胞因子反应偏向为特征的增强的寄生虫抗原特异性Th1细胞反应以及随之而来的更强的抗锥虫免疫球蛋白G2a抗体反应相关。经TGF-β1预处理的感染小鼠的锥虫诱导的B细胞过度增殖显著减少。此外,本文提供的证据表明外源性TGF-β1可激活巨噬细胞,这可能有助于控制寄生虫。总体而言,这些数据表明外源性TGF-β1具有免疫刺激作用,可能通过涉及固有免疫反应的机制诱导对刚果锥虫感染的部分保护。