Helminths as architects of trained tolerance: implications for human health

Helminths infect nearly 2 billion people worldwide and are a major cause of chronic morbidity in low-resource regions. Unlike bacterial and viral pathogens that elicit protective memory, helminths actively remodel host immunity to enable their years-long persistence and reinfection. We put forward the concept of 'trained tolerance', which describes the durable yet reversible system-wide immunological programme helminths exert on the host to promote their own survival. In humans, this altered immune set point shapes host responses to concurrent challenges, including cancer immunity, allergy, autoimmunity, coinfections and vaccine effectiveness. Here, we outline research priorities, including defining species-specific immune correlates of protection versus tolerance, integrating longitudinal cohorts and controlled human infection studies with single-cell and spatial profiling, establishing standardised biomarker panels to track immune recalibration after parasite clearance and evaluating the impact of anthelmintic treatment prior to immunisation campaigns to restore germinal centre function and durable protection.