寄生于体内的线虫:能通过线虫糖链预防自身免疫性疾病吗?
Worms to the rescue: can worm glycans protect from autoimmune diseases?
机构信息
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, the Netherlands.
出版信息
IUBMB Life. 2010 Apr;62(4):303-12. doi: 10.1002/iub.304.
Autoimmune and autoinflammatory diseases represent a significant health burden, especially in Western societies. For the majority of these diseases, no cure exists. Recently, research on parasitic worms (helminths) has demonstrated great potential for whole worms, their eggs or their excretory/secretory proteins in down-regulating inflammatory responses both in vitro and in vivo, in various disease models and, in some cases, even in clinical trials. The worms are thought to induce Th2 and regulatory T cells, interfere with Toll-like receptor (TLR) signaling and to down-regulate Th17 and Th1 responses. The molecular mechanisms underlying the worms' ability to modulate the host immune response are not well understood, and many hypotheses have been proposed to explain the observed immune modulation. Increasing evidence suggests that carbohydrate structures (glycans), for example, phosphorylcholine-modified glycans or Galbeta1-4(Fucalpha1-3)GlcNAc- (Lewis X, Le(X)) containing glycans, expressed by the worms contribute to these modulating properties by their interaction with antigen presenting cells. Helminths express a broad variety of protein- and lipid-linked glycans on their surface and on secretory products. These glycans differ in amount and composition and several of these structures are species specific. However, worms also express glycan antigens that are found in a wide variety of different species. Some of these "common" worm glycans are particularly interesting with regard to regulating host responses, because they have the potential to interact with C-type lectins on dendritic cells and thereby may interfere with T-cell polarization. Helminths and helminth-derived molecules form a novel and promising group of therapeutics for autoinflammatory diseases. However, much has to be learned about the molecular mechanisms behind the helminth-mediated antiinflammatory properties. This review will describe some of the emerging evidence in selected disease areas as well as discuss the putative role of glycans in helminth-mediated immunosuppression.
自身免疫和自身炎症性疾病是一个重大的健康负担,尤其是在西方国家。对于这些疾病中的大多数,目前还没有治愈方法。最近,对寄生虫(蠕虫)的研究表明,在各种疾病模型中,无论是在体外还是体内,蠕虫及其卵或排泄/分泌蛋白都具有很强的下调炎症反应的潜力,而且在某些情况下,甚至在临床试验中也具有潜力。这些蠕虫被认为能诱导 Th2 和调节性 T 细胞,干扰 Toll 样受体(TLR)信号,并下调 Th17 和 Th1 反应。蠕虫调节宿主免疫反应的分子机制尚不清楚,已经提出了许多假说来解释观察到的免疫调节。越来越多的证据表明,碳水化合物结构(糖),例如,磷酸胆碱修饰的聚糖或 Galbeta1-4(Fucalpha1-3)GlcNAc-(Lewis X,Le(X))含有聚糖,通过与抗原呈递细胞相互作用,对这些调节特性做出贡献。蠕虫在其表面和分泌产物上表达广泛的蛋白质和脂类连接的聚糖。这些聚糖在数量和组成上有所不同,其中一些结构具有物种特异性。然而,蠕虫还表达存在于多种不同物种中的糖抗原。其中一些“常见”的蠕虫糖抗原在调节宿主反应方面特别有趣,因为它们有可能与树突状细胞上的 C 型凝集素相互作用,从而可能干扰 T 细胞极化。蠕虫及其衍生分子形成了一组治疗自身炎症性疾病的新型有前途的治疗方法。然而,在蠕虫介导的抗炎特性的分子机制方面,还有很多需要了解。本文将描述在选定疾病领域的一些新出现的证据,并讨论聚糖在蠕虫介导的免疫抑制中的潜在作用。