title: The placental protein syncytin-1 impairs antiviral responses and exaggerates inflammatory responses to influenza.
abstract: BACKGROUND
  Pregnancy increases susceptibility to influenza. The placenta releases an immunosuppressive endogenous retroviral protein syncytin-1. We hypothesised that exposure of peripheral monocytes (PBMCs) to syncytin-1 would impair responses to H1N1pdm09 influenza.
  
  
  RESULTS
  Recombinant syncytin-1 was produced. PBMCs from non-pregnant women (n=10) were exposed to H1N1pdm09 in the presence and absence of syncytin-1 and compared to responses of PBMCs from pregnant women (n=12). PBMCs were characterised using flow cytometry, release of interferon (IFN)-α, IFN-λ, IFN-γ, IL-10, IL-2, IL-6 and IL-1β were measured by cytometric bead array or ELISA. Exposure of PBMCs to H1N1pdm09 resulted in the release of IFN-α, (14,787 pg/mL, 95% CI 7311-22,264 pg/mL) IFN-λ (1486 pg/mL, 95% CI 756-2216 pg/mL) and IFN-γ (852 pg/mL, 95% CI 193-1511 pg/mL) after 48 hours. This was significantly impaired in pregnant women (IFN-α; p<0.0001 and IFN-λ; p<0.001). Furthermore, in the presence of syncytin-1, PBMCs demonstrated marked reductions in IFN-α and IFN-λ, while enhanced release of IL-10 as well as IL-6 and IL-1β.
  
  
  CONCLUSIONS
  Our data indicates that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza.
authors.affiliation: Mothers and Babies Research Centre and Hunter Medical Research Institute, The University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Tolosa
authors.affiliation: Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, The University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Kristy S
authors.initials: KS
authors.lastname: Parsons
authors.affiliation: Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, The University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
authors.affiliation: Mothers and Babies Research Centre and Hunter Medical Research Institute, The University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Smith
authors.affiliation: Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, The University of Newcastle, Newcastle, NSW, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, NSW, Australia.
authors.forename: Peter A B
authors.initials: PA
authors.lastname: Wark
mesh_terms: D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D015686:Gene Products, env / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000821:virology; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D055815:Young Adult
chemical_list: D016207:Cytokines; D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin
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