Worms to the rescue: can worm glycans protect from autoimmune diseases?

Abstract

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.