ES-62, a therapeutic anti-inflammatory agent evolved by the filarial nematode Acanthocheilonema viteae

Abstract

Filarial nematodes cause long-term infections in hundreds of millions of people. A significant proportion of those affected develop a number of debilitating health problems but, remarkably, such infections are often unnoticed for many years. It is well known that parasitic worms modulate, yet do not completely inhibit, host immunological pathways, promoting their survival by limiting effective immune mechanisms. Such immunoregulation largely depends on molecules released by the worms, termed excretory-secretory products (ES). One of these products is the molecule ES-62, which is actively secreted by the rodent filarial nematode Acanthocheilonema viteae. ES-62 has been shown to exert anti-inflammatory actions thorough its phosphorylcholine (PC)-containing moiety on a variety of cells of the immune system, affecting intracellular signalling pathways associated with antigen receptor- and TLR-dependent responses. We summarise here how ES-62 modulates key signal transduction elements and how such immunomodulation confers protection to mice subjected to certain experimental models of inflammatory disease. Finally, we discuss recent results showing that it is possible to synthetise small molecule analogues (SMAs) that mimic the anti-inflammatory properties of ES-62, opening an exciting new drug development field in translational medicine.

Keywords: Cell signalling; ES-62; Helminth; Hygiene hypothesis; IL-17; Immunomodulation.