title: Investigating the impact of Echinococcus multilocularis vesicular fluid on human cells from healthy blood donors.
abstract: OBJECTIVE
  Alveolar echinococcosis (AE) is a severe chronic helminthic disease that mimics slow-growing liver cancer. Previous studies using murine models suggest that Echinococcus multilocularis (Em) metacestodes have developed mechanisms which impair the natural inflammatory host response. The aim of this study was to investigate in vitro the impact of Em vesicular fluid (VF) on monocytes, monocytes derived dendritic cells and lymphocytes from healthy blood donors.
  
  
  METHODS
  First, assays were performed to investigate whether or not Em-VF influences monocyte-derived dendritic cell (MoDC) differentiation and maturation. Monocytes during differentiation and immature MoDCs were exposed to Em-VF. The effect of Em-VF was assessed using flow cytometry (CD86, CD83, CD80) and immune assays (IL-10 and TGFβ). Second, assays were performed to investigate the interaction between Em-VF, peripheral blood monocyte cells (PBMC) and Toll-like Receptor (TLR) agonists (LPS, PolyIC, R848 and CpG). PBMC were stimulated by each of the TLR agonists with and without Em-VF. The subsequent TGFβ production was assessed.
  
  
  RESULTS
  Exposure to Em-VF had bearing on both differentiation and maturation of MoDC, but only partially. A decrease in the expression of co-stimulatory molecules was observed; however, levels of immune-regulatory cytokines were stable. PBMC exposed simultaneously to Em-VF and LPS induced a significant increase of TGFβ (p<0.05, Wilcoxon signed-rank test). Further experiments showed that TGFβ production was lymphocyte-dependent.
  
  
  CONCLUSIONS
  The assays performed confirmed that Em-VF influences the host immune response. However, only minor changes were observed when investigating the Em-VF impact on cells from healthy blood donors. Assays with TLR agonists suggested that co-stimulation with LPS reinforces the response of healthy blood donors exposed to Em-VF.
authors.affiliation: Parasitology-Mycology Department, Besançon University Hospital, F-25000 Besançon, France; Franche-Comté University, F-25000 Besançon, France; CNRS 6249 /UMR "Chrono-environnement", F-25000 Besançon, France. Electronic address: apbellanger@gmail.com.
authors.forename: Anne-Pauline
authors.initials: AP
authors.lastname: Bellanger
authors.affiliation: Inserm U1098, EFS Bourgogne Franche-Comté, University of Franche-Comté, IFR133 Besançon, France.
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Pallandre
authors.affiliation: Infection Control Department, Besançon University Hospital, F-25000 Besançon, France.
authors.forename: Houssein
authors.initials: H
authors.lastname: Gbaguidi-Haore
authors.affiliation: Parasitology-Mycology Department, Besançon University Hospital, F-25000 Besançon, France; CNRS 6249 /UMR "Chrono-environnement", F-25000 Besançon, France.
authors.forename: Jenny
authors.initials: J
authors.lastname: Knapp
authors.affiliation: Parasitology-Mycology Department, Besançon University Hospital, F-25000 Besançon, France.
authors.forename: Noémie
authors.initials: N
authors.lastname: Malézieux
authors.affiliation: Parasitology-Mycology Department, Besançon University Hospital, F-25000 Besançon, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Lignon
authors.affiliation: Inserm U1098, EFS Bourgogne Franche-Comté, University of Franche-Comté, IFR133 Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: Parasitology-Mycology Department, Besançon University Hospital, F-25000 Besançon, France; Franche-Comté University, F-25000 Besançon, France; CNRS 6249 /UMR "Chrono-environnement", F-25000 Besançon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Millon
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004443:Echinococcosis; D004444:Echinococcosis, Hepatic / Q000276:immunology* / Q000469:parasitology; D048210:Echinococcus multilocularis / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007249:Inflammation; D016753:Interleukin-10 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007136:Immunoglobulins; D016753:Interleukin-10; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D000097802:CD83 Antigen; C497964:CD86 protein, human; C508609:IL10 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human
keywords: Dendritic cells; Echinococcus multilocularis; Lymphocytes; Monocytes; TGFß; Vesicular fluid