Regulatory T cell responses in areas where Plasmodium falciparum and Schistosoma haematobium infections coexist: disentangling co-infection

没有必要强调热带地区疟疾感染的重要性及其在全球造成的破坏性影响，每年造成200多万人死亡。恶性疟原虫在加蓬高度流行，在Lambarene研究地区进行的卫生调查数据表明，恶性疟原虫和蠕虫感染经常共存（Adegnika等人，2007年）。众所周知，蠕虫感染具有很强的免疫调节作用，可能影响对不相关抗原的反应（Maizels & Yazdanbakhsh, 2003; Su et al. 2006）。有趣的是，20世纪70年代的早期研究表明，疟疾与免疫抑制有关，从而影响对不相关抗原的反应（Greenwood et al. 1972）。近年来，越来越多的证据表明，恶性疟原虫不仅在疟疾发作期间，而且在无症状时也能诱导调节反应（Bejon et al. 2007; Walther et al. 2005）。调节性T细胞受到了广泛的关注，似乎对维持一个良好平衡的免疫系统至关重要（Sakaguchi et al. 2008）。它们的功能障碍与明显的炎症反应有关，而它们的明显表达会损害对疫苗或传入病原体的有效免疫反应（Couper et al. 2008）。事实上，一些成功的寄生虫似乎有能力诱导调节性T细胞，以提高它们在宿主体内的存活率（Walther et al. 2005）。关于调节性T细胞的性质的信息很少，它可能参与蠕虫感染期间经常看到的免疫抑制，也不知道它们在恶性疟原虫感染期间的功能。更重要的是，我们对Treg细胞在合并感染期间的活性一无所知。在加蓬的Lambarene，我们进行了十多年的研究，并掌握了关于恶性疟原虫和包括血血吸虫在内的蠕虫感染的流行病学的准确信息。目前的建议是研究恶性疟原虫和嗜血杆菌共感染过程中的调节性T细胞。它将利用加蓬已经建立的技术来评估调节性T细胞的表型和功能。这些数据可能具有重要意义，有助于理解临床共感染的重要性，并为在寄生虫经常共流行的地区测试新的候选疫苗（包括疟疾疫苗）铺平道路。

There is no need to emphasize the importance of malarial infections in the tropics and its devastating effect globally resulting in over two million deaths per year. P. falciparum is highly endemic in Gabon and figures from the health surveys in the study area of Lambarene have shown that P. falciparum and helminth infections frequently co-exist (Adegnika et al. 2007). It is known that helminth infections have strong immune modulatory effects, which may affect responses to unrelated antigens (Maizels & Yazdanbakhsh, 2003; Su et al. 2006) interestingly, early studies in 1970's had indicated that malaria is associated with immune suppression whereby responses to unrelated antigens were affected (Greenwood et al. 1972). In recent years, evidence is accumulating for the ability of P. falciparum parasites to induce regulatory responses not only during malarial episode but also when asymptomatic (Bejon et al. 2007; Walther et al. 2005).Regulatory T cells have received much attention, and seem to be central to the maintenance of a well balanced immune system (Sakaguchi et al. 2008). Their dysfunction is associated with overt inflammatory reactions, whereas their overt expression can compromise effective immune responses to vaccines or to incoming pathogens (Couper et al. 2008). In fact some successful parasites appear to have the ability to induce regulatory T cells in order to enhance their survival within their host (Walther et al. 2005).There is little information on the nature of regulatory T cells that might be involved in the immune suppression that is often seen during helminth infections, nor is there much known of their function during P. falciparum infections. More importantly, there is nothing known about the activity of Treg cells during coinfection.In Lambarene, Gabon, we have been conducting studies for more than a decade and have accurate information on the epidemiology of P. falciparum and helminth infections which include Schistosoma haematobium. The current proposal will study regulatory T cells during P. falciparum and S. haematobium coinfections. It will utilize techniques already established in Gabon to assess the phenotype and function of regulatory T cells.Such data could have important implications for understanding the significance of coinfections clinically and for paving the way for testing new candidate vaccines, including those for malaria, in areas where helminths are often coendemic.