Characterization and ligand binding properties of a fatty acid-and retinol-binding protein (Hp-FAR-2) from Heligmosomoides polygyrus

Abstract

Parasitic nematodes are major pathogens of humans, animals, and plants, contributing to global health challenges and substantial agricultural losses. Fatty acid-and retinol-binding proteins (FARs), secreted by parasitic nematodes, are believed to play key roles in host–pathogen interactions, including immune modulation and nutrient acquisition. In this study, we characterize a FAR protein from the gastrointestinal nematode Heligmosomoides polygyrus, Hp-FAR-2. Hp-FAR-2, unlike FARs from Caenorhabditis elegans, Steinernema carpocapsae, and Ancylostoma ceylanicum, did not influence immunity or survival in a Drosophila melanogaster infection model, suggesting functional divergence within the FAR family. Competitive lipid-binding assays revealed a preference for omega-3 and omega-6 polyunsaturated fatty acids, indicating selective binding to bioactive lipids that may modulate immunity. Using RAW 264.7 macrophages, we found that Hp-FAR-2 suppresses the expression of both M1-associated (TNF-α, IL-6) and M2-associated (Chil3) markers during polarization, implicating it as a broad immunomodulator that may inhibit inflammatory responses and tissue repair mechanisms to promote chronic infection. Our findings support a model in which Hp-FAR-2 disrupts host lipid signaling and immune function to favor parasite persistence, suggesting its potential role in the excretory/secretory products of H. polygyrus. These findings enhance our understanding of FAR-mediated host manipulation and may inform the development of novel anthelmintic or immunoregulatory therapies.