Nematodes immunomodulatory mechanisms and possible clinical application.

Helminths have evolved complex immunomodulatory mechanisms that enable chronic infection while minimizing host damage. This review summarizes recent advances in understanding nematode-derived molecules with therapeutic potential. The phosphorylcholine-modified glycoprotein ES-62 from Acanthocheilonema viteae exemplifies pathway-selective immune regulation and has inspired small-molecule analogues for inflammatory diseases. Ancylostoma duodenale secretes protease inhibitors, anticoagulants, and anti-inflammatory proteins that reveal targets for immune and hemostatic modulation. Anisakis pegreffii exerts context-dependent immune control via dendritic cell tolerization, macrophage polarization, and regulatory T-cell expansion. The cystatin Al-CPI from Ascaris lumbricoides reprograms dendritic cell metabolism, induces immune tolerance, and shows efficacy in colitis and allergy models. Brugia malayisecretes proteins that modulate antigen presentation, complement activation, and cytokine signaling. Together, these findings highlight helminth-derived compounds as blueprints for precision immunotherapies that restore immune homeostasis with minimal side effects.