Glycans modulate immune responses in helminth infections and allergy.
Infections of humans and animals by parasitic helminths share key features with atopic diseases, such as allergic asthma. Both diseases lead to the induction of high levels of Th2- type cytokines associated with abundant IgE production and eosinophilia. This immunological association has raised strong interest in the nature of the molecules that promote Th2 and regulatory T cell responses, and the molecular mechanism. Complex carbohydrates are potent inducers of Th2 responses, and carbohydrate antigens (Ags) can stimulate the production of different classes of glycan-specific antibodies (Abs), including Th2 associated IgG but also non-specific IgE. In this review we focus on the immunological responses towards glycan Ags derived from allergens and parasitic helminths, especially schistosomes. Biological effects of carbohydrate Ags are dependent on recognition of these Ags by carbohydrate- binding proteins (lectins). Cell-surface C-type lectin receptors (CLRs), such as DCSIGN, L-SIGN, the mannose receptor, macrophage galactose binding lectin, and other lectins, such as the soluble collectins and galectin-3, recognize particular glycan Ags of schistosomes and allergens, which may contribute to orchestrate Th2 associated adaptive responses. Remarkably, schistosomes express 'self glycan' Ags that are recognized by CLRs on DCs, whose principal function is thought to capture self-glycan Ags and generate regulatory T-cells to induce tolerance to these Ags. By expressing such self-glycan Ags, schistosomes may deceive the host immune system to their own benefit. The host protects itself against too much damage by down-regulating helminth-induced Th2 immune responses, and may thus simultaneously be protected against excessive Th2 cell-mediated allergic responses.
van Die
Irma
I
Glycoimmunology Group, Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Cummings
Richard D
RD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D006373:Helminthiasis / Q000276:immunology* / Q000469:parasitology*; D006376:Helminths / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D011134:Polysaccharides / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D011134:Polysaccharides