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

## TL;DR

This study explores a protein from a parasitic worm that binds specific fatty acids and suppresses immune responses, potentially aiding the worm's survival in hosts.

## Contribution

The study characterizes Hp-FAR-2, a novel fatty acid-binding protein from Heligmosomoides polygyrus, and reveals its unique immunomodulatory effects.

## Key findings

- Hp-FAR-2 preferentially binds omega-3 and omega-6 polyunsaturated fatty acids.
- Hp-FAR-2 suppresses both M1 and M2 macrophage polarization markers.
- Hp-FAR-2 does not affect immunity or survival in a Drosophila infection model.

## 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.

Parasitic worms infect billions of people worldwide and cause long-term, chronic infections that remain a major public health challenge. To survive inside their hosts, these parasites release secreted proteins that alter immune responses and help the worms persist. One protein family unique to nematodes is the fatty acid- and retinol-binding proteins (FARs), which are thought to bind host lipids and interfere with normal signaling. In this study, we investigated a previously uncharacterized FAR protein from the intestinal parasite Heligmosomoides polygyrus, called Hp-FAR-2. We found that Hp-FAR-2 binds selectively to omega-3 and omega-6 fatty acids, which are important regulators of inflammation and immunity. When tested in fruit flies, Hp-FAR-2 did not affect survival or immune responses, suggesting that its function may be specific to mammalian hosts. In experiments with mouse macrophages, Hp-FAR-2 reduced the expression of genes linked to both inflammation and tissue repair. These findings show that Hp-FAR-2 can target key immune pathways by binding host lipids, which may promote parasite survival. Understanding these mechanisms could help identify new strategies for controlling worm infections or even inspire therapies for inflammatory diseases.