title: Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity.
abstract: The phagocyte respiratory burst is crucial for innate immunity. The transfer of electrons to oxygen is mediated by a membrane-bound heterodimer, comprising gp91phoxand p22phoxsubunits. Deficiency of either subunit leads to severe immunodeficiency. We describe Eros (essential for reactive oxygen species), a protein encoded by the previously undefined mouse genebc017643, and show that it is essential for host defense via the phagocyte NAPDH oxidase. Eros is required for expression of the NADPH oxidase components, gp91phoxand p22phoxConsequently,Eros-deficient mice quickly succumb to infection.Erosalso contributes to the formation of neutrophil extracellular traps (NETS) and impacts on the immune response to melanoma metastases.Erosis an ortholog of the plant protein Ycf4, which is necessary for expression of proteins of the photosynthetic photosystem 1 complex, itself also an NADPH oxio-reductase. We thus describe the key role of the previously uncharacterized protein Eros in host defense.
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Thomas
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, England, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: John M
authors.initials: JM
authors.lastname: Sowerby
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, England, UK.
authors.forename: Mercedes
authors.identifier: 0000-0002-3477-9695
authors.initials: M
authors.lastname: Pardo
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: Jatinder K
authors.initials: JK
authors.lastname: Juss
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, England, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Goulding
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, England, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: van der Weyden
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: Daniel
authors.identifier: 0000-0003-2681-518X
authors.initials: D
authors.lastname: Storisteanu
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, England, UK.
authors.forename: Ananth
authors.initials: A
authors.lastname: Prakash
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: Marion
authors.identifier: 0000-0001-5005-1664
authors.initials: M
authors.lastname: Espéli
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: Shaun
authors.identifier: 0000-0002-5282-9334
authors.initials: S
authors.lastname: Flint
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: James C
authors.identifier: 0000-0001-5711-9385
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, England, UK.
authors.forename: Kim
authors.identifier: 0000-0001-8499-9832
authors.initials: K
authors.lastname: Hoenderdos
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, England, UK.
authors.forename: Leanne
authors.identifier: 0000-0002-2241-8120
authors.initials: L
authors.lastname: Kane
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, England, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Harcourt
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, England, UK.
authors.forename: Subhankar
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, England, UK.
authors.forename: Yagnesh
authors.identifier: 0000-0003-0366-901X
authors.initials: Y
authors.lastname: Umrania
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, England, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Antrobus
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge CB2 0XY, England, UK.
authors.forename: James A
authors.identifier: 0000-0002-0248-1632
authors.initials: JA
authors.lastname: Nathan
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, England, UK.
authors.forename: David J
authors.identifier: 0000-0001-9490-0306
authors.initials: DJ
authors.lastname: Adams
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, England, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Bateman
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, England, UK.
authors.forename: Jyoti S
authors.identifier: 0000-0003-0881-5477
authors.initials: JS
authors.lastname: Choudhary
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: Paul A
authors.identifier: 0000-0001-7035-8997
authors.initials: PA
authors.lastname: Lyons
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: Alison M
authors.identifier: 0000-0002-6697-8648
authors.initials: AM
authors.lastname: Condliffe
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: Edwin R
authors.identifier: 0000-0002-4230-9677
authors.initials: ER
authors.lastname: Chilvers
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK kgcs2@cam.ac.uk gd1@sanger.ac.uk.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, England, UK.
authors.forename: Gordon
authors.identifier: 0000-0003-0022-965X
authors.initials: G
authors.lastname: Dougan
authors.affiliation: Department of Medicine, University of Cambridge, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, England, UK.
authors.forename: Kenneth G C
authors.identifier: 0000-0003-3829-4326
authors.initials: KG
authors.lastname: Smith
mesh_terms: D000818:Animals; D003573:Cytochrome b Group / Q000032:analysis / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000032:analysis / Q000502:physiology; D009504:Neutrophils / Q000276:immunology; D010586:Phagocytes / Q000502:physiology*; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst / Q000502:physiology*
chemical_list: D003573:Cytochrome b Group; C000621863:Eros protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C515614:Cyba protein, mouse