Acquired immunity mechanisms in sheep infected with Nematodirus oiratianus: key genes and host responses

Background Controlling gastrointestinal nematode infections poses a major challenge in intensive farming, worsened by rising anthelmintic resistance. Developing innovative control strategies is critical. Sheep acquired immunity to Nematodirus oiratianus offers a valuable model for dissecting host-nematode interactions, though underlying immune mechanisms remain unclear. Methods This study employed multi-omics analyses (transcriptome and proteome) of lamb duodenum across infection stages, validated by RT-qPCR, iELISA, histopathological staining (HE), and electron microscopy. Results and conclusions Infection triggered early immune activation mediated by intestinal epithelial cells. Key differentially expressed genes included CLDN18 , CCL19 , FGB , and Muc5ac , potentially linking to parasite expulsion. Early-stage pathway enrichment in cancer, chemokine signaling, and phagosome function enhanced intestinal barrier integrity and immune cell recruitment. Late-stage upregulation of CCL chemokines directly impacted nematode survival. Intestinal villi shedding was also correlated with parasite clearance. These findings unravel potential mechanisms of acquired immunity against Nematodirus oiratianus , highlighting novel therapeutic targets (e.g., epithelial barrier regulators, chemokine networks) and vaccine candidates for nematode control in livestock.