Dual role of Echinococcus granulosus antigen B: a parasite lipoprotein with immunoregulatory and lipid acquisition properties in myeloid cells

Abstract

The larval stage of Echinococcus granulosus causes cystic echinococcosis, a chronic infection that tightly modulates the host´s immune response. Adapted to a nutrient-rich environment, the parasite has lost the ability to synthesize fatty acids and cholesterol de novo , instead relying on the uptake of host-derived lipids through the action of specialized proteins. Antigen B (EgAgB), the main larval lipoprotein, belonging to the cestode-specific hydrophobic ligand-binding protein family, is believed to facilitate the uptake and transport of host lipids essential for the parasite. It is exported to host tissues and resembles HDL in physicochemical properties and anti- inflammatory effects on innate cells. Our investigation on EgAgB´s biological activities revealed that both native and recombinant lipoproteins induced a modest activation of dendritic cell (DC), attributed to LPS contamination, while suppressing LPS-induced cytokine (IL1b, IL6, IL12, IFNb) and nitric oxide production in DC and macrophages (MQ) by disrupting TLR4 dimerization. In the current work, we confirmed that in an LPS stimulation context, EgAgB does not affect ATP potentiation of IL1b secretion linked to inflammasome activation in MQ. Moreover, EgAgB outcompeted LPS for binding to DC/MQ and inhibited LPS-driven cytokine release more effectively than HDL. Binding assays and light scattering approaches confirmed EgAgB’s superior LPS-binding ability, supported by docking analysis showing a defined LPS-binding interface in the EgAgB8/1 subunit. Regarding lipid handling, fluorescence assays showed that EgAgB acquired cholesterol from HDL as well as from MQ, suggesting additional interactions with host cells that may have functional relevance and are currently under investigation. Our findings reveal novel activities for EgAgB: an extracellular LPS scavenger property that dampens TLR4-mediated inflammation in myeloid cells and a cholesterol uptake capacity from host lipoproteins/cells. Altogether, results support a dual role of EgAgB in E. granulosus biology, contacting host components to acquire essential lipids while contributing to parasite protection from host inflammation.