Integrated transcriptomic and metabolomic profiling reveals dynamic host–pathogen interactions during Theileria annulata infection in bovine erythrocytes and leukocytes

Abstract Theileria annulata causes tropical theileriosis in cattle, yet the molecular basis of host–parasite crosstalk across intracellular stages remains incompletely defined. We combined RNA sequencing and untargeted metabolomics to profile paired uninfected and infected bovine leukocytes (schizont stage) and erythrocytes (piroplasm stage), together with purified schizonts and piroplasms. Integrated analyses revealed pronounced, cell type-specific reprogramming. Infected leukocytes showed activation of immune signalling, amino acid metabolism and energy-producing pathways, consistent with leukocyte transformation, whereas infected erythrocytes preferentially engaged glutathione metabolism and redox homeostasis. Parasite stage comparisons uncovered extensive transcriptional and metabolic rewiring, including stage-biased expression of mitochondrial components, antioxidant systems and putative stage-regulated transcription factors. These coherent host–parasite adaptations likely facilitate parasite survival and persistence within distinct cellular niches. This work delineates a stage-resolved multi-omics landscape of T. annulata infection spanning host and parasite compartments and identifies signalling and metabolic pathways that merit functional validation as candidates for improved diagnostics and targeted interventions against bovine tropical theileriosis.