The placental derived protein syncytin-1 impairs antiviral responses and exaggerates inflammatory responses to influenza — ASN Events
  1. Schedule
  2. Poster Session 2
  3. The placental derived protein syncytin-1 impairs antiviral responses and exaggerates inflammatory responses to influenza

The placental derived protein syncytin-1 impairs antiviral responses and exaggerates inflammatory responses to influenza (#147)

Peter PW Peter Wark 1 , Jorge M. JT Tolosa 2 , Kristy Parsons 1 , Roger Smith 2
  1. Centre for Asthma and Respiratory Disease, HMRI, New Lambton, NSW, Australia
  2. Mother's and Babies Research Centre, HMRI, New Lambton, NSW, Australia

Pregnant women are particularly susceptible to influenza and the recent pandemic shows that poor outcomes including death continue to occur. The placenta releases the endogenous retroviral envelope protein syncytin-1, which has been demonstrated to have immunosuppressive properties. We hypothesised that exposure of peripheral monocytes (PBMCs) from healthy women to syncytin-1 would impair antiviral responses to pandemic H1N109pdm, reflecting the impaired immune response seen in PBMCs from pregnant women.

Methods: Recombinant syncytin-1 was produced in BL21 (DE3) E. coli cells by using the pET-28b-based expression vector, purified on Hitrap IMAC HP column then Sephadex column. We exposed PBMCs from non-pregnant women to H1N109pdm in the presence and absence of syncytin-1 and compared the early immune response with that of PBMCs from pregnant women exposed to H1N109pdm.  PBMCs were characterised using flow cytometry, with a separate panel to determine dendritic cell and lymphocyte lineages. Release of interferon (IFN)-α, IFN-γ, IL-10, IL-2, IL-6 and IL-1β were measured by cytometric bead array, IFN-λ by ELISA.

Results; Exposure of PBMCs to H1N109pdm by 48 hours resulted in the release of IFN-α/λ/γ, however PBMCs from pregnant women had significantly reduced release of IFN-α/λ. In the presence of syncytin-1, PBMCs from non-pregnant women behaved like those from pregnant women with a marked reduction in IFN-α/λ. In addition they demonstrated enhanced release of IL-10 as well as IL-6 and IL-1β.

Conclusions; Exposureof PBMCsto syncytin-1 led to a marked impairment in antiviral IFN responses. In addition it led to the release of potentially immunosuppressive IL-10, but pro-inflammatory IL-6 and IL-1β. Our data indicates for the first time that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza as well as other viral and bacterial infections.