title: Enteric helminth-induced type I interferon signaling protects against pulmonary virus infection through interaction with the microbiota.
abstract: BACKGROUND
  Helminth parasites have been reported to have beneficial immunomodulatory effects in patients with allergic and autoimmune conditions and detrimental consequences in patients with tuberculosis and some viral infections. Their role in coinfection with respiratory viruses is not clear.
  
  
  OBJECTIVE
  Here we investigated the effects of strictly enteric helminth infection with Heligmosomoides polygyrus on respiratory syncytial virus (RSV) infection in a mouse model.
  
  
  METHODS
  A murine helminth/RSV coinfection model was developed. Mice were infected by means of oral gavage with 200 stage 3 H polygyrus larvae. Ten days later, mice were infected intranasally with either RSV or UV-inactivated RSV.
  
  
  RESULTS
  H polygyrus-infected mice showed significantly less disease and pulmonary inflammation after RSV infection associated with reduced viral load. Adaptive immune responses, including TH2 responses, were not essential because protection against RSV was maintained in Rag1-/-and Il4rα-/-mice. Importantly, H polygyrus infection upregulated expression of type I interferons and interferon-stimulated genes in both the duodenum and lung, and its protective effects were lost in both Ifnar1-/-and germ-free mice, revealing essential roles for type I interferon signaling and microbiota in H polygyrus-induced protection against RSV.
  
  
  CONCLUSIONS
  These data demonstrate that a strictly enteric helminth infection can have remote protective antiviral effects in the lung through induction of a microbiota-dependent type I interferon response.
authors.affiliation: MRC-Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom; Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: McFarlane
authors.affiliation: MRC-Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom; Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: McSorley
authors.affiliation: MRC-Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Davidson
authors.affiliation: MRC-Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom; Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Fitch
authors.affiliation: National Health Service Lothian, Simpson Centre for Reproductive Health, Edinburgh, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Errington
authors.affiliation: MRC-Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Mackenzie
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Lausanne, Switzerland.
authors.forename: Eva S
authors.initials: ES
authors.lastname: Gollwitzer
authors.affiliation: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Chris J C
authors.initials: CJC
authors.lastname: Johnston
authors.affiliation: Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester, United Kingdom.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: MacDonald
authors.affiliation: Airway Disease Infection Section, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma and Centre for Respiratory Infection, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Edwards
authors.affiliation: Global Health Institute, École Polytechnique, Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Harris
authors.affiliation: Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, CHUV, Lausanne, Switzerland.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Marsland
authors.affiliation: Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Maizels
authors.affiliation: MRC-Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom; Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: Jurgen.Schwarze@ed.ac.uk.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schwarze
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D002478:Cells, Cultured; D060085:Coinfection; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007370:Interferon Type I / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000469:parasitology; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology*; D009351:Nematospiroides dubius / Q000276:immunology*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D015398:Signal Transduction; D017206:Strongylida Infections / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology
chemical_list: D000947:Antigens, Helminth; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D053633:Receptor, Interferon alpha-beta
keywords: Heligmosomoides polygyrus; Respiratory syncytial virus; helminths; microbiome; type I interferon