LAUSR

In every encounter between different species, critical recognition processes inform and direct the response on each side. In settings such as parasitism, the interaction is exploited by an invading organism to manipulate its host and facilitate its establishment. Frequently, the signals dispatched by parasites have evolved from physiological pathways governing their own development and reproduction, adapted for a novel function environment of the host. There is no better example than found in an exciting new report, in PNAS (1), that pheromone-like ascaroside signaling molecules, released from an intestinal nematode parasite, act to block the host immune response mode that would be most damaging to the worm. Nematode roundworms, together with cestode tapeworms and trematode flukes, collectively termed helminths, are near-ubiquitous parasites in low-resource countries (2). Immunity to helminths is dependent on the type 2 arm of the immune response, orchestrated by Th2 helper lymphocytes and their cytokines (such as IL-4 and IL-5), driving IgE antibodies and innate effector cells such as macrophages and eosinophils (3). The same set of players mediate allergic reactions, suggesting that allergy may be the consequence of a poorly regulated immune system with an overzealous type 2 response. Globally, there is an inverse correlation between helminth prevalence and inflammatory disorders such as allergy and autoimmune disease, suggesting that helminths can dampen type 2 immunity across the board (4). Where deliberate helminth infection of humans has been trialed, some patients experience alleviation of symptoms, but this therapeutic strategy faces numerous challenges (5), and increasing emphasis is placed on laboratory models to identify pathways of parasite immunomodulation and the molecular players involved (6). Accordingly, a fascinating palette of molecular mediators from helminths are now being defined (7). In the case Fig. 1. Nb parasites release pheromones such as ascr#7, found in smES materials; these act on other members of the same species (Top Right) while also modulating the host type 2 immune response and alarmin cytokines such as IL-33. The type 2 response in allergy to house dust mite (HDM) or ovalbumin (OVA) activates type 2 helper T cells (Th2) and innate lymphoid cells (ILC2) which express the IL-33 receptor (ST2) and release cytokines such as IL-4 (that drives IgE production) and IL-5 (which induces eosinophils). If ascr#7 is coadministered to mice with allergen, expression of IL-33 and ST2 is abated, the type 2 response is suppressed, and macrophage expression of the suppressive cytokine IL-10 is enhanced.