Parasitic worms threaten human, animal and plant health by infecting people, livestock and crops worldwide. Animals and plants share an anciently evolved innate immune system. Parasites modulate this immune system by secreting proteins to maintain their parasitic lifestyle. This thesis describes how venom-allergen-like proteins (VAPs) that both animal- and plant-parasitic nematodes release into their hosts, modulate host innate immunity. On the one hand we found that one particular secreted VAP from the potato cyst nematode can activate host defenses in tomato plants, opening an opportunity for plant breeders to generate novel nematode-resistant cultivars. We showed that plants make more efficiently use of their limited repertoire of immune receptors by guarding common virulence targets of multiple unrelated plant pathogens. While on the other hand, we describe how VAPs may be used by parasites to suppress the host defense responses mediated by extracellular immune receptors. In short, this fundamental study contributes to our understanding of the molecular basis of persistent infections by parasitic nematodes in plants and in animals.