title: Echinococcus granulosus antigen B impairs human dendritic cell differentiation and polarizes immature dendritic cell maturation towards a Th2 cell response.
abstract: 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-kappaB, 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.
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Rachele
authors.initials: R
authors.lastname: Riganò
authors.forename: Brigitta
authors.initials: B
authors.lastname: Buttari
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Profumo
authors.forename: Elena
authors.initials: E
authors.lastname: Ortona
authors.forename: Federica
authors.initials: F
authors.lastname: Delunardo
authors.forename: Paola
authors.initials: P
authors.lastname: Margutti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mattei
authors.forename: Antonella
authors.initials: A
authors.lastname: Teggi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sorice
authors.forename: Alessandra
authors.initials: A
authors.lastname: Siracusano
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018949:Antigens, CD1 / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000502:physiology; D048209:Echinococcus granulosus / Q000276:immunology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D016328:NF-kappa B / Q000032:analysis; D010766:Phosphorylation; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D051940:B7-2 Antigen; D016207:Cytokines; D007136:Immunoglobulins; D053592:Interleukin-1 Receptor-Associated Kinases; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D000097802:CD83 Antigen; C514022:antigen B, Echinococcus granulosus