Exploratory Toxicogenomic Analysis of Parasite-Related Th2 Immune Response

Helminth parasites infect mammalian hosts through complex life cycles, mostly triggering T helper type 2 (Th2) immune responses characterized by interleukin-4 (IL4), interleukin-5 (IL5), and interleukin-13 (IL13) production. Environmental chemical exposures may modulate these immune pathways, potentially affecting infection outcomes. Using The Comparative Toxicogenomics Database (CTD), we analyzed chemical–gene interactions affecting IL4, IL5, and IL13 genes to identify chemicals capable of modulating Th2 immunity and their associated expression profiles. Accordingly, a total of 818 chemicals can interact with IL4, IL5 and/or IL13, with 145 chemicals showing the potential of affecting all three genes. These 145 chemicals include air pollutants (8.3%), allergens (2.7%), bioactive molecules (8.3%), industry-related chemicals (14.5%), medicinal drugs (21.4%), metal and metal-containing chemicals (8.3%), pesticides (3.4%), plant compounds (12.4%), and others (20.7%). We observed a greater number of chemicals associated with increased (n = 95) gene expression compared to decreased (n = 14) gene expression, suggesting a Th2 pathway hyperactivation caused by chemicals capable of affecting IL4, IL5 and IL13. Eight classes of parasitic diseases were observed among chemical-associated conditions. Environmental chemicals extensively modulate Th2 immune responses through diverse molecular mechanisms. The trend concerning upregulation of Th2 pathways may enhance antiparasitic protection but, on the other hand, could predispose individuals to allergic diseases, among other Th2-related conditions. These exploratory findings suggest that chemical pollution may influence the susceptibility and pathogenesis of helminth infections and highlight the need for the incorporation of exposome-based approaches in parasitology research.