Fasciolagigantica Recombinant Bone Morphogenetic Protein (FgBMP) Modulates Various Functions of Buffalo Peripheral...

Fasciolosis, a disease induced by liver fluke infection, poses a major threat to the livestock industry. The emergence of drug resistance and the lack of commercial vaccines necessitate the development of novel control strategies. Studies on helminth immunoregulatory molecules have become a key research focus. Bone morphogenetic proteins (BMPs), ligand members of the TGF-β superfamily, have been identified in Fasciola gigantica and designated FgBMPs, and are hypothesized to regulate host immune responses. To explore the effects of FgBMP on hosts, the mechanistic actions of FgBMP-1 on buffalo peripheral blood mononuclear cells (PBMCs) were investigated to preliminarily elucidate host-parasite interactions. Molecular docking predicted strong binding between FgBMP-1 and buffalo BMP receptors. Immunostaining using specific monoclonal antibodies revealed the tissue distribution of FgBMP-1, confirming its expression in adult worms, juvenile worms, and excretory-secretory products of F. gigantica (FgESP). Recombinant FgBMP-1 (rFgBMP-1) bound to buffalo PBMCs and significantly suppressed cell proliferation, migration, and phagocytosis while enhancing nitric oxide production. Transcriptional analysis showed that rFgBMP-1 downregulated IFN-γ and IL-10 transcription, whereas it upregulated IL-4 and TGF-β transcription. Transcriptome analysis revealed that rFgBMP-1 may activate the classical TGF-β and MAPK pathways independently or synergistically. Additionally, rFgBMP-1 may modulate host immune responses via crosstalk with the Th17 differentiation and Toll-like receptor signaling pathways. Therefore, FgBMP-1 may mediate immunosuppression in buffalo PBMCs via activation of the TGF-β pathway, thereby refining the theoretical understanding of parasite immune evasion.