The unfolded protein response pathway mediates ovalbumin-induced innate immune response in Caenorhabditis elegans

Ovalbumin (OVA), the major allergen in egg white, is used as a model allergen in the studies of food allergy. Previous studies have confirmed that OVA can induce innate immune responses in Caenorhabditis elegans (C. elegans), and the expression of genes related to the unfolded protein response (UPR) pathway was also significantly changed in transcriptome sequencing. However, whether OVA induces innate immunity in C. elegans by activating the UPR pathway, and the specific mechanism underlying this process, remains unclear. In this study, the expression of UPR reporter genes (hsp-3, hsp-4) was used to verify whether the UPR pathway was activated during OVA-induced innate immunity in C. elegans. Subsequently, the signal transduction pathways in the UPR pathway were investigated using RNA interference (RNAi) and gene knockout mutants. Our results demonstrated that OVA treatment significantly upregulated the expression of UPR reporter genes hsp-4 and hsp-3 in C. elegans, confirming that the UPR pathway was effectively activated, and this activation involved both the canonical and noncanonical UPR pathways. Mechanistically, the canonical UPR mediated OVA-induced protein homeostasis maintenance and innate immunity initiation through the skn-1-pek-1 axis, while the noncanonical UPR exerted effects through octr-1-ABU pathways. In conclusion, this study clearly reveals the molecular mechanism by which OVA triggers innate immunity in C. elegans via activating the UPR pathway. These findings provide novel insights into the initiation mechanism by which food allergens trigger innate immunity.