title: The Schistosoma mansoni T2 ribonuclease omega-1 modulates inflammasome-dependent IL-1β secretion in macrophages.
abstract: The T2 ribonuclease omega-1 is a powerful Th2-inducing factor secreted by the eggs of the blood fluke Schistosoma mansoni. Omega-1 can modulate pattern recognition receptor-induced inflammatory signatures and alter antigen presentation by dendritic cells. Recent findings have suggested that component(s) contained in or secreted by S. mansoni eggs (soluble egg antigen) can also enhance IL-1β secretion by dendritic cells stimulated with pattern recognition receptor ligands. Here we show that omega-1 enhances IL-1β secretion in macrophages stimulated with Toll-like receptor 2 ligand, and propose omega-1 as the factor in soluble egg antigen capable of regulating inflammasome activity. This effect is dependent on the C-type lectin receptor Dectin-1, caspase-8 and the ASC inflammasome adaptor protein, highlighting the ability of omega-1 to regulate multiple pattern recognition receptor signalling pathways. These mechanistic insights into manipulation of host immunity by a parasite product have implications for the design of anti-inflammatory therapeutic drugs.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP Cambridge, UK.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ferguson
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Newland
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP Cambridge, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Gibbs
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tourlomousis
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP Cambridge, UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Fernandes dos Santos
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Meghana N
authors.initials: MN
authors.lastname: Patel
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP Cambridge, UK.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Hall
authors.affiliation: Centre for Cell Death, Cancer, and Inflammation (CCCI), UCL Cancer Institute, University College London, London, UK.
authors.forename: Henning
authors.initials: H
authors.lastname: Walczak
authors.affiliation: Research Center Borstel, D-23845 Borstel, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schramm
authors.affiliation: helminGuard, D-23867 Suelfeld, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Haas
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP Cambridge, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Dunne
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP Cambridge, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Cooke
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP Cambridge, UK. Electronic address: pz206@cam.ac.uk.
authors.forename: Paola
authors.initials: P
authors.lastname: Zaccone
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004527:Egg Proteins / Q000378:metabolism*; D004722:Endoribonucleases / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D012550:Schistosoma mansoni / Q000201:enzymology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D000099181:Dectin-1
chemical_list: D000947:Antigens, Helminth; D053181:Caspase 8; D004527:Egg Proteins; D004722:Endoribonucleases; D058847:Inflammasomes; D053583:Interleukin-1beta; D037181:Lectins, C-Type; D000099181:Dectin-1; C587622:omega-1 antigen, Schistosoma mansoni; C022543:ribonuclease T(2)
keywords: IL-1β; IPSE/alpha-1; Inflammasome; Omega-1; Schistosoma mansoni antigens; T2 ribonuclease