title: Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor.
abstract: Omega-1, a glycosylated T2 ribonuclease (RNase) secreted by Schistosoma mansoni eggs and abundantly present in soluble egg antigen, has recently been shown to condition dendritic cells (DCs) to prime Th2 responses. However, the molecular mechanisms underlying this effect remain unknown. We show in this study by site-directed mutagenesis of omega-1 that both the glycosylation and the RNase activity are essential to condition DCs for Th2 polarization. Mechanistically, we demonstrate that omega-1 is bound and internalized via its glycans by the mannose receptor (MR) and subsequently impairs protein synthesis by degrading both ribosomal and messenger RNA. These experiments reveal an unrecognized pathway involving MR and interference with protein synthesis that conditions DCs for Th2 priming.
authors.affiliation: Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Everts
authors.forename: Leonie
authors.initials: L
authors.lastname: Hussaarts
authors.forename: Nicole N
authors.initials: NN
authors.lastname: Driessen
authors.forename: Moniek H J
authors.initials: MH
authors.lastname: Meevissen
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schramm
authors.forename: Alwin J
authors.initials: AJ
authors.lastname: van der Ham
authors.forename: Barbara
authors.initials: B
authors.lastname: van der Hoeven
authors.forename: Thomas
authors.initials: T
authors.lastname: Scholzen
authors.forename: Sven
authors.initials: S
authors.lastname: Burgdorf
authors.forename: Markus
authors.initials: M
authors.lastname: Mohrs
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Pearce
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Hokke
authors.forename: Helmut
authors.initials: H
authors.lastname: Haas
authors.forename: Hermelijn H
authors.initials: HH
authors.lastname: Smits
authors.forename: Maria
authors.initials: M
authors.lastname: Yazdanbakhsh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004722:Endoribonucleases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010063:Ovum / Q000737:chemistry; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000201:enzymology*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D011956:Receptors, Cell Surface; D004722:Endoribonucleases; C022543:ribonuclease T(2)