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.
Highlights
The advantage of genetic diversity has ensured the success of sexual reproduction in evolution, but in placental mammals it comes with the inherent dilemma that the maternal immune system must tolerate the existence of the semi-allogenic foetus/placenta that expresses both self and non-self antigens[1]
Peripheral Blood Mononuclear Cell (PBMC) from pregnant and non-pregnant women were cultured with a strain of influenza isolated during the 2009 swine flu pandemic (H1N1pdm09) or cultured in media only
PBMCs from non-pregnant women demonstrated a robust IFN-α (14,787 pg/mL, 95% CI 7311–22,264 pg/mL) and IFN-λ (1486 pg/mL, 95% CI 756–2216 pg/mL) response to H1N1pdm09 (Fig. 1A-C,) compared to media alone after 48hours of exposure
Summary
The advantage of genetic diversity has ensured the success of sexual reproduction in evolution, but in placental mammals it comes with the inherent dilemma that the maternal immune system must tolerate the existence of the semi-allogenic foetus/placenta that expresses both self (maternal) and non-self (paternal) antigens[1]. Recent advances have demonstrated the importance of co-ordinating immune responses between pathogen detection (non-self antigens) by the innate immune system and activation or suppression of adaptive immune responses. In this regard dendritic cells (DCs) are an essential link in coordinating these immune responses in health and in pregnancy[5,6]. The human placenta is unique amongst tissues in having the highest expression of human endogenous retroviruses These are evolutionary fossils, which at some ancient time point have infected germ line cells. We determined that human syncytin-1 released from the placenta suppresses maternal immune responses demonstrating it’s potential to play a role in maternal/ foetal tolerance[9]. We hypothesised that exposure of peripheral monocytes (PBMCs) to syncytin-1 would impair responses to H1N1pdm influenza.
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