Epigenetic changes induced by parasitic worms and their excretory-secretory products

Parasitic worms are pathogens of major medical and veterinary importance. They have evolved highly effective and sophisticated strategies of immune system manipulation, typically involving actively excreted/secreted (E-S) products. These molecules dampen and regulate the host immune responses that would otherwise result in parasite expulsion, thereby enabling the worms to survive in the host for many years, and they can also help prevent the potentially serious tissue damage that the worms can induce. Reflecting these E-S product-associated anti-inflammatory activities, there is also increasing evidence that parasitic worms and their products may serendipitously protect against allergic and autoimmune conditions and in addition, comorbidities of ageing that are associated with inflammatory responses, like type 2 diabetes and obesity. Research in this area has to date generally focused on identifying the cellular and effector targets of immunomodulation induced by the worm E-S products. However, increasing evidence that they can induce stably imprinted phenotypes of haematopoietic and stromal cells which promote their long-lasting survival has recently ignited interest in the ability of the molecules to epigenetically rewire cells to 'resolve and repair' phenotypes. Here, we review and discuss these new data in the context of their potential for exploitation in identifying novel gene signatures for the development of advanced and safe therapeutics for chronic inflammatory diseases.