Echinococcus granulosus antigen B: an immunomodulatory lipid-binding protein at the host-parasite interface

Abstract

Cystic echinococcosis is a chronic infection caused by the larvae of the parasite Echinococcus granulosus s.l. (hydatid), which establishes in the viscera of the intermediate hosts (mainly domestic ungulates but also humans). Antigen B (EgAgB) is the major hydatid lipoprotein, which size and biochemical composition are similar to that of the plasma HDL3. EgAgB apolipoproteins are encoded by 5 genes (EgAgB1-5) belonging to the cestode-specific family of hydrophobic ligands binding proteins (HLBP) of unknown function. EgAgB was described as a parasite immunomodulator based on its ability to interfere with dendritic cell (DC) activation in vitro; however, these studies used denatured EgAgB preparations. Herein, we found that immunopurified EgAgB (native and the recombinant EgAgB1 expressed in insect cells) inhibited LPS-driven cytokine (IL6, IL12, IFNβ) secretion and NO generation, but not CD86 and CD40 expression, in macrophages (MC) and DC. In addition, EgAgB bound to DC in a TLR4-independent manner and inhibited LPS binding to DC and MC, suggesting it might neutralize LPS in the milieu as HDL3 does. Interestingly, in a mixed lymphocyte reaction EgAgB seemed to favour a Th2-type differentiation profile. On the other hand, since HDL-induced cholesterol efflux was found to be linked to immunomodulation effects in innate cells, we hypothesize that EgAgB might uptake cholesterol from MC and DC, influencing cell response to inflammatory stimuli. In fact, preliminary studies revealed that EgAgB could promote cholesterol efflux from THP-1 and J774 cells. This finding is interesting since cestodes are unable to synthesize cholesterol and need to uptake it from the host. Identification of cell receptors involved in EgAgB-induced cholesterol efflux and their putative link to immunomodulation effects are in progress. Overall, our work shed light on the biological properties of a novel HLBP that might explain the remarkable ability of hydatid to adapt to host immune response.