Despite inducing a strong host cellular and humoral immune response, the helminth Echinococcus granulosus is a highly successful parasite that develops, progresses, and ultimately causes chronic disease. Although surgery remains the preferred therapeutic option, pharmacological research now envisages antihelminthic strategies. To understand the mechanisms that E. granulosus uses to escape host immunosurveillance and promote chronic infection, we investigated how two hydatid cyst components, purified antigen B (AgB) and sheep hydatid fluid (SHF), act on host dendritic cell (DC) differentiation from monocyte precursors and how they influence maturation of DC that have already differentiated. We evaluated the immunomodulatory potential of these antigens by performing immunochemical and cytofluorimetric analyses of monocyte-derived DCs from healthy human donors. During monocyte differentiation, AgB and SHF downmodulated CD1a expression and upregulated CD86 expression. Compared with immature DCs differentiated in medium alone (iDCs), AgB-and SHF-differentiated cells stimulated with lipopolysaccharide included a significantly lower percentage of CD83؉ cells (P < 10 ؊4 ) and had weaker costimulatory molecule expression. When stimulated with AgB and SHF, iDCs matured and primed lymphocytes towards the Th2 response typical of E. granulosus infection. SHF and particularly AgB reduced the production of interleukin-12p70 (IL-12p70) and tumor necrosis factor alpha in lipopolysaccharide-stimulated iDCs. Anti-IL-10 antibodies increased the levels of IL-12p70 secretion in AgB-and SHF-matured DCs. AgB and SHF induced interleukin-1 receptor-associated kinase phosphorylation and activated nuclear factor-B, suggesting that Toll-like receptors could participate in E. granulosus-stimulated DC maturation. These results suggest that E. granulosus escapes host immunosurveillance in two ways: by interfering with monocyte differentiation and by modulating DC maturation.

The larval stage of Echinococcus granulosus causes cystic echinococcosis, a neglected infectious disease that constitutes a major public health problem in developing countries. Despite being under constant barrage by the immune system, E. granulosus modulates antiparasite immune responses and persists in the human hosts with detectable humoral and cellular responses against the parasite. In vitro and in vivo immunological approaches, together with molecular biology and immunoproteomic technologies, provided us exciting insights into the mechanisms involved in the initiation of E. granulosus infection and the consequent induction and regulation of the immune response. Although the last decade has clarified many aspects of host-parasite relationship in human cystic echinococcosis, establishing the full mechanisms that cause the disease requires more studies. Here, we review some of the recent developments and discuss new avenues in this evolving story of E. granulosus infection in man.

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The human plasma protein ␤ 2 -glycoprotein I (␤ 2 -GPI) is the most common target for antiphospholipid antibodies associated with thrombotic events in chronic disorders related to endothelial cell dysfunction. Crucial information is needed to clarify why this self-abundant protein is targeted by autoimmune responses. In this study, we investigated whether oxidative modification of ␤ 2 -GPI, either spontaneous in culture wells or induced by treatment with H 2 O 2 , renders this selfprotein able to activate immature monocyte-derived dendritic cells (DCs) from healthy human donors. Oxidized ␤ 2 -GPI caused DCs to mature so that CD83 appeared and CD80, CD86, human leukocyte antigen-D region related (HLA-DR), and CD40 increased. The interaction between oxidized ␤ 2 -GPI and DCs specifically stimulated these cells to secrete interleukin 12 (IL-12), IL-1␤, IL-6, IL-8, tumor necrosis factor ␣ (TNF-␣), and IL-10. Oxidized ␤ 2 -GPI-stimulated DCs had increased allostimulatory ability and primed naive T lymphocytes, thus inducing T helper 1 (Th1) polarization. The interaction between oxidized ␤ 2 -GPI and DCs involved interleukin-1 receptor associated kinase (IRAK) phosphorylation and nuclear factor B (NFB) activation. Pretreatment of ␤ 2 -GPI with the antioxidant ␣-tocopherol prevented DC maturation. These findings show that human oxidized ␤ 2 -GPI, probably by interacting with a member of the Toll-like receptor (TLR) family, causes DCs to mature. Because this key ␤ 2 -GPI function requires oxidative modification, in several chronic disorders related to endothelial cell dysfunction oxidative stress might trigger the "autoimmune spiral. Introduction␤ 2 -glycoprotein I (␤ 2 -GPI), a human plasma protein that binds to negatively charged phospholipids, is the most common target for antiphospholipid antibodies (aPLs). These autoantibodies are associated with thrombotic events in systemic lupus erythematosus 1 and primary antiphospholipid antibody syndrome 2,3 and are proatherogenic. 4 ␤ 2 -GPI also activates lipoprotein lipase, 5 lowers the triglyceride level, 6 and binds to oxidized low-density lipoprotein (LDL) 7 and to nonself particles or apoptotic bodies to allow their clearance. [8][9][10] Another property of ␤ 2 -GPI is its ability to bind at the monocyte surface, thus promoting tissue factor and thereby increasing the risk of thrombotic events. 11 ␤ 2 -GPI can also be expressed on the endothelial cell membrane 12 and on macrophages. 13 Among the several candidate ␤ 2 -GPI cell receptors, annexin II, megaline, and apolipoprotein E receptor 2Ј (apoER2Ј) are involved in activating endothelial cells and platelets. [14][15][16] Recent findings demonstrate that anti-␤ 2 -GPI antibodies react with their antigen probably in association with a member of the Toll-like receptor (TLR)/interleukin 1 (IL-1) receptor family on the endothelial cell surface and directly induce activation. 17,18 Once bound to endothelial cells, ␤ 2 -GPI offers suitable epitopes targeting circulating anti-␤ 2 -GPI antibodies that affect cell functions a...

Cystic echinococcosis (CE) is a widespread chronic endemic helminthic disease caused by infection with metacestodes of the tapeworm Echinococcus granulosus. CE affects humans and has a worldwide prevalence of approximately six million. In this review, we discuss current findings in diagnosis and clinical management of CE and new concepts relating to E. granulosus molecules that directly modulate the host immune responses favouring a strong anti-inflammatory response and perpetuating parasite survival in the host. New insights into the molecular biology of E. granulosus will improve considerably our knowledge of the disease and will provide new potential therapeutic applications to treat or prevent inflammatory immune-mediated disease.