Exploring the functional and immunological diversity of the fatty acid-binding protein (FABP) family in Fasciola hepatica

The liver flukes Fasciola hepatica and Fasciola gigantica cause fasciolosis, a zoonotic disease of major health and livestock importance. To evade host immunity, these parasites secrete immunomodulatory molecules, including fatty acid-binding proteins (FABPs), which are essential for parasite survival by mediating fatty acid uptake and transport, and by exerting anti-inflammatory effects that promote immune evasion and chronic infection. This study investigates the roles of F. hepatica FABPs' in nutrient acquisition, immune modulation, and parasite survival, assessing their potential as vaccine, diagnostic, and therapeutic targets. We cloned all seven FhFABP isoforms and expressed six recombinantly in yeast. Gene expression analysis showed stage-specific patterns, with the highest levels in adult flukes. Isoform-specific analysis further highlighted stage-dependent expression dynamics, and functional characterization revealed distinct fatty acid-binding properties, suggesting adaptive roles in parasite survival. We assessed IgG responses in infected sheep, finding peak titer against FhFABP5 at 6-8 weeks post-infection (WPI) and a strong, prolonged response to FhFABP4, lasting 6-12 weeks. These results highlight FhFABPs as immunogenic targets for diagnostics or vaccines. Additionally, FhFABPs differentially modulated the activity of human monocyte-derived dendritic cells. Our findings emphasize the multifaceted roles of FhFABPs in nutrient acquisition and immune modulation, underscoring their potential as targets for vaccines, diagnostics, and anti-inflammatory therapies.