The Placental Protein Syncytin-1 Impairs Antiviral Responses and Exaggerates Inflammatory Responses to Influenza |
| |
| Authors: | Jorge M Tolosa Kristy S Parsons Philip M Hansbro Roger Smith Peter A B Wark |
| |
| Institution: | 1. Mothers and Babies Research Centre and Hunter Medical Research Institute, The University of Newcastle, Newcastle, NSW, Australia.; 2. Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, The University of Newcastle, Newcastle, NSW, Australia.; 3. Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, NSW, Australia.; University of Geneva, SWITZERLAND, |
| |
| Abstract: | BackgroundPregnancy 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.Methods and FindingsRecombinant 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.ConclusionsOur data indicates that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza. |
| |
| Keywords: | |
|
|
