A potential metabolic and immunoregulatory role of antigen B lipoprotein in Echinococcus granulosus biology: similarities and differences with plasma HDL

Abstract

The larva of the parasite Echinococcus granulosus causes cystic echinococcosis, a chronic infection 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 and transporting essential lipids. One of these proteins, antigen B (EgAgB), is a member of the cestode-specific hydrophobic ligand-binding protein family with diagnostic value. In its native form, EgAgB is a 230 kDa lipoprotein containing ~50% lipids in mass. We demonstrated that EgAgB binds to monocytes and macrophages in a dose-dependent manner using receptors shared with HDL. In addition, we recently found that EgAgB discharges cholesterol from macrophages, mimicking HDL capacity. Since HDL-induced cholesterol efflux on innate cells seems to be linked to modulation, EgAgB effects on the inflammatory activation of macrophages were studied in comparison with HDL. When co-administered with LPS, EgAgB inhibited macrophages activation decreasing: in vitro IL-1beta, IL-6, IL-12, IFN-gamma and .NO and in vivo IL-6 and IL-12 (together with a potentiation of IL-10) at 4 h post-injection, and MHC-II, CD40 and CD86 in resident macrophages at 24 h post-injection in the peritoneal cavity. Furthermore, EgAgB and LPS exhibited in vitro as well as in vivo mutual interference in cell recognition and/or effects, indicating the involvement of a common cell receptor and/or the ability of EgAgB to bind LPS. In this scenario, a putative EgAgB-LPS interaction supporting a scavenger activity, as recently described for HDL, is being explored. Contrasting with EgAgB, in the assayed conditions HDL did not modulate in vitro LPS-activation of macrophages, suggesting differences between their interactions with macrophages. Overall, our results support a potential metabolic and immunoregulatory role of EgAgB in E. granulosus biology, mimicking some HDL properties.