Shared roles between Echinococcus granulosus antigen B and vertebrates HDL: immunoregulation and lipid acquisition properties

Abstract

The larva of Echinococcus granulosus causes cystic echinococcosis, a chronic viscera infection (mainly liver) implying a tight control of host immunity. Its location in a medium rich in nutrients shaped the parasite's metabolism, losing de novo fatty acid and cholesterol synthesis pathways together with the expression of proteins capable of capturing/transporting essential lipids. Antigen B (EgAgB), the main larva lipoprotein, is a member of the cestode-specific hydrophobic ligand-binding protein family, being exported through unknown mechanisms to host tissues. EgAgB resembles vertebrates HDL in molecular size, lipid:protein ratio, lipids heterogeneity and a-helix predominance on its apolipoproteins. Moreover, EgAgB and HDL share anti-inflammatory properties on innate cells. This work goes deeper into EgAgB's biological activities, in comparison with HDL. Results showed that native EgAgB and HDL modulate LPS-driven macrophage activation, with lower EgAgB concentration needed to reach similar IL-6 inhibition. In competition assays, both lipoproteins decreased LPS binding to macrophages, suggesting EgAgB interacts with LPS interfering with its cellular recognition and inflammatory consequences, as HDL does. Besides, in direct binding analyses, EgAgB bound LPS to a larger extent than HDL, interaction favoured by the presence of LBP. An EgAgB scavenger activity of enteric LPS that reaches the liver could contribute to decrease harmful consequences of LPS-driven inflammation in the parasite vicinity, a physiological role that HDL plays in this organ. The EgAgB ability to scavenger other PAMPs or DAMPS requires further studies. On the other hand, since EgAgB carries host cholesterol and plasma lipoproteins can exchange lipids, we analysed EgAgB's ability to uptake cholesterol from HDL. EgAgB captured fluorescent cholesterol from previously loaded HDL, suggesting additional interactions between EgAgB and HDL for parasite cholesterol acquisition. Altogether, results support a dual role of EgAgB in E. granulosus biology, contacting host components to acquire essential lipids while contributing to protecting the parasite from host inflammation.