Peripheral blood mononuclear cell-driven cytokine and transcription factors induction confers resistance to Haemonchus contortus in Black Bengal goats

Haemonchus contortus is a major threat to small ruminant health and productivity. Although early Th2 cytokine and transcription factor expression confers protection in naturally resistant breeds, the immune basis of resistance in Black Bengal goats (BBG) remains unexplored. We compare early PBMC-mediated cytokine and transcriptional responses and their direct effects on larval motility between naive and primed BBG kids during the first seven days of infection. Kids were primed with 2000 L₃ weekly for four weeks or left naive, then challenged with 10,000 L₃. Two kids per group were sacrificed on each time point. Whole blood was collected pre-mortem for differential counts and PBMC isolation, while abomasal mucosa and draining LN were harvested for histology and RNA extraction. Primed kids exhibited a 58 % reduction in abomasal L₄ burden by day 7, elevated PCV (p < 0.05), and a threefold greater increase in LN weight compared to naive kids. Histopathology revealed significantly enhanced eosinophil and neutrophil infiltration in abomasal mucosa of primed kids. Cytokine and gene expression assay showed early upregulation of Interleukin (IL)-4, IL-5, IL-13, IL-33, MCP-1, CXCL-1, TLR-2, and GAL-14 (p < 0.05). In vitro, co-culture with primed PBMCs reduced L₃ motility compared to naive PBMCs (p < 0.01) and L₃ pretreated with primed PBMCs resulted in a 60 % reduction in fecal egg counts by week 5 (p < 0.001). This is the first study to integrate daily PBMC transcriptomics with functional motility and infectivity assays in BBGs. The findings identify novel biomarkers, inform selective breeding and immunoprophylactic strategies for sustainable parasite control.