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Parasitic nematodes face multiple challenges in their lives, most notably physical barriers and immune defenses associated with host species. An evolutionary arms race underlies all host-parasite interactions in which hosts have constrained the detrimental impact of parasites, while the latter have learned how to overcome host responses to establish and reproduce. This constant negotiation has resulted in highly specialized interspecific relationships, characterized by complex molecular dialogues between hosts and parasites. The often chronic and non-fatal nature of nematode infections, which may persist for a decade in their hosts, is due to their highly evolved abilities to hide from the host immune system and to modulate or suppress it to their own advantage.