A potential metabolic and immunoregulatory role of antigen B lipoprotein in Echinococcus granulosus biology

Abstract

The parasite Echinococcus granulosus causes cystic echinococcosis, a chronic infection that implies a strong control of host immunity. Moreover, its location in a medium rich in nutrients shaped parasite's metabolism, loosing de novo fatty acid and cholesterol synthesis pathways, together with the expression of proteins capable of capturing and transporting essential lipids. Antigen B (EgAgB) is a lipoprotein member of the hydrophobic ligand binding protein family (HLBP), specific of cestodes, with important diagnostic value. EgAgB effects were studied on innate immune cells, employing immunopurified EgAgB preparations: the native lipoprotein and the recombinant rEgAgB8/1 (the main apolipoprotein in native EgAgB, expressed in insect cells). This work provides the first evidence of EgAgB ability to exchange lipids with host cells, by discharging cholesterol from human and murine macrophages similarly to HDL. In addition, EgAgB inhibited macrophage activation induced by LPS in vitro, decreasing IL1β, IL6, IL12p40 and •NO. In vivo EgAgB reduced the LPS-induced IL6 secretion, together with an IL10 potentiation, at 4 h post-injection in the peritoneal cavity of BALB/c mice. Interestingly, EgAgB itself showed a pro-inflammatory effect, leading to peritoneal neutrophil, eosinophil and monocyte recruitment at 4 and/or 24 h post-stimulation. However, myeloid peritoneal cells showed a poorly activated phenotype (MHC-II, CD86, CD40) in comparison with LPS. Moreover, EgAgB decreased in vivo LPS-induced activation of resident macrophages (MHC-II for LPM; CD40 and CD86 for SPM), dendritic cells (CD86) and recruited monocytes (CD86). On the other hand, EgAgB and LPS exhibited in vitro as well as in vivo mutual interference in cell recognition and/or effects, suggesting the involvement of a common cellular receptor and/or EgAgB ability to scavenge LPS. Taken together, our results support a potential metabolic and immunoregulatory role of EgAgB in E. granulosus biology.