Immunomodulation by Parasitic Helminths and its Therapeutic Exploitation

Parasitic worms are able to survive in their mammalian hosts for many years due to their ability to manipulate the immune response by secreting immunomodulatory products. These products differ between species of helminths, but they share common mechanisms of action such as modulation of Toll-like receptor pathways and induction of regulatory immune responses along with pro-inflammatory Th2 responses, what is often termed as a ‘modified Th2 response’. Interestingly, it is increasingly clear that, reflecting the anti-inflammatory actions of such worm-derived immunomodulators, there is an inverse correlation between helminth infection and autoimmune diseases in the developing world. As the decrease in helminth infections due to increased sanitation has correlated with an alarming increase in prevalence of such disorders in industrialised countries, this "Hygiene Hypothesis" has led to the proposal that worms and their secreted products offer a novel platform for the development of safe and effective strategies for the treatment of allergic and autoimmune disorders. We summarize here, the current understanding of helminth-derived molecules with immunomodulatory activity and their associated cellular and molecular mechanisms that act in the host to modulate the immune response. In addition, we reveal how these findings have been applied in the clinic and in research to develop novel therapies for allergy and autoimmune diseases, like asthma, rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis.

Keywords: Allergy, antigen presenting cell, autoimmunity, cystatin, dendritic cell, ES-62, FOXP3, helminth, helminth-based therapy, hygiene hypothesis, IL-10, immunomodulation, modified Th2 response, NFκB, regulatory T cell, Soluble Egg Antigen, TGFβ, Th1/Th2 responses, Th17 responses, Toll-like receptors.