ReviewSecretory products of helminth parasites as immunomodulators

- Interest in secretory helminth products has grown over 30-40 years.
- Immunomodulation is increasingly characterized and arguably now the main focus.
- The molecular basis of immunomodulation by secretory products is becoming known.
- Secretory products are being tested as novel anti-inflammatory therapeutics.

Parasitic helminths release molecules into their environment, which are generally referred to as excretory-secretory products or ES. ES derived from a wide range of nematodes, trematodes and cestodes have been studied during the past 30-40 years, their characterization evolving from simple biochemical procedures such as SDS-PAGE in the early days to sophisticated proteomics in the 21st century. Study has incorporated investigation of ES structure, potential as vaccines, immunodiagnostic utility, functional activities and immunomodulatory properties. Immunomodulation by ES is increasingly the area of most intensive research with a number of defined helminth products extensively analyzed with respect to the nature of their selective effects on cells of the immune system as well as the molecular mechanisms, which underlie these immunomodulatory effects. As a consequence, we are now beginning to learn the identities of the receptors that ES employ and are increasingly acquiring detailed knowledge of the signalling pathways that they interact with and subvert. Such information is contributing to the growing idea that the anti-inflammatory properties of a number of ES products makes them suitable starting points for the development of novel drugs for treating human inflammatory disease.

Secretory products of helminth parasites modulate the activities of a number of cells of the immune system, blocking pro-inflammatory/Th1/Th17 responses and inducing anti-inflammatory/Th2 responses.133