title: Fasciola hepatica Kunitz type molecule decreases dendritic cell activation and their ability to induce inflammatory responses.
abstract: The complete repertoire of proteins with immunomodulatory activity in Fasciola hepatica (Fh) has not yet been fully described. Here, we demonstrated that Fh total extract (TE) reduced LPS-induced DC maturation, and the DC ability to induce allogeneic responses. After TE fractionating, a fraction lower than 10 kDa (F<10 kDa) was able to maintain the TE properties to modulate the DC pro- and anti-inflammatory cytokine production induced by LPS. In addition, TE or F<10 kDa treatment decreased the ability of immature DC to stimulate the allogeneic responses and induced a novo allogeneic CD4+CD25+Foxp3+ T cells. In contrast, treatment of DC with T/L or F<10 kDa plus LPS (F<10/L) induced a regulatory IL-27 dependent mechanism that diminished the proliferative and Th1 and Th17 allogeneic responses. Finally, we showed that a Kunitz type molecule (Fh-KTM), present in F<10 kDa, was responsible for suppressing pro-inflammatory cytokine production in LPS-activated DC, by printing tolerogenic features on DC that impaired their ability to induce inflammatory responses. These results suggest a modulatory role for this protein, which may be involved in the immune evasion mechanisms of the parasite.
authors.affiliation: Department of Biological Chemistry, Faculty of Chemical Sciences, National University of Cordoba, CIQUIBIC-CONICET, Córdoba, Argentina.
authors.forename: Cristian R
authors.initials: CR
authors.lastname: Falcón
authors.affiliation: Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Cordoba, CIBICI-CONICET, Córdoba, Argentina.
authors.forename: Diana
authors.initials: D
authors.lastname: Masih
authors.affiliation: Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Cordoba, CIBICI-CONICET, Córdoba, Argentina; Foundation for the advancement of Medicine, Córdoba, Argentina.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Gatti
authors.affiliation: Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Cordoba, CIBICI-CONICET, Córdoba, Argentina.
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: Sanchez
authors.affiliation: Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Cordoba, CIBICI-CONICET, Córdoba, Argentina.
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Motrán
authors.affiliation: Department of Clinical Biochemistry, Faculty of Chemical Sciences, National University of Cordoba, CIBICI-CONICET, Córdoba, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Cervi
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005210:Fasciola hepatica / Q000166:cytology / Q000201:enzymology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000502:physiology; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015801:Helminth Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors