Environmental factors that regulate host-helminth interactions.

Soil-transmitted helminths (STHs) infect over a billion people worldwide. Individual outcomes vary, ranging from subclinical, mild infections to recurrent or severe disease. Emerging evidence reveals that susceptibility to STH infection reflects a multilayered integration of past and present environmental factors. At mucosal surfaces, STHs activate type 2 immune, epithelial, and neuronal circuits, while microbial- and diet-derived signals promote homeostasis. Environmental signals tune the transcriptional programs that control these events, shaping interleukin-13-driven effector functions required for worm expulsion. Concurrently, infection and inflammation history imprint immune and epithelial compartments, leading to durable epigenetic remodeling and altering responsiveness to STHs upon reexposure. Understanding how environmental factors impact host-helminth interactions offers new opportunities to predict susceptibility and design interventions that enhance anti-helminth immunity.