UC Riverside

Lipids are essential biomolecules that influence a wide range of physiological and immune processes across diverse organisms. Polyunsaturated fatty acids and their downstream metabolites are increasingly recognized as central regulators of host immunity across species. My research focuses on uncovering how lipid signaling shapes host-pathogen interactions in nematodes and insects. Parasitic nematodes, such as Heligmosomoides polygyrus, secrete fatty acid– and retinol- binding proteins that manipulate host lipid signaling pathways. One such protein, Hp-FAR-2, was characterized and found to selectively bind omega-3 and omega-6 polyunsaturated fatty acids and broadly suppress macrophage polarization and inflammatory gene expression in host macrophages. These findings suggest that Hp-FAR-2 facilitates parasite persistence by interfering with host immune lipid pathways. Building on these insights, oxylipin signaling was investigated in Drosophila melanogaster and found that supplementation with arachidonic acid stimulated eicosanoid production through cyclooxygenase, lipoxygenase, and cytochrome P450 pathways, and enhanced antimicrobial peptide expression during bacterial challenge. To further link lipid metabolism to immunity, CG1583, a secretory phospholipase A₂ (PLA₂) in Drosophila, was shown to hydrolyze phosphatidylethanolamine and phosphatidylglycerol and significantly improve fly survival following bacterial infection. Together, these findings demonstrates that lipids have evolved as a molecular interface between nematodes and insects. By revealing how lipids influence these pathways, my work highlights the central role of lipids in shaping immune strategies throughout metazoan evolution.