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.
