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BACKGROUND Pregnant women are considered to have a high risk for influenza virus infection, although little is known about the biological reasons for this risk. Antiviral immunity is critical during influenza virus infection, and understanding the changes that occur during pregnancy and the effect of vaccination is essential for improving health outcomes for mother and baby. METHODS Peripheral blood mononuclear cells (PBMCs) were isolated from 26 healthy, nonpregnant women and 28 healthy pregnant women and cultured with 2009 pandemic influenza A virus subtype H1N1 (H1N1/09). Protein concentrations of interferon α (IFN-α), IFN-λ, and IFN-γ were measured from culture supernatant. Messenger RNA expression of protein kinase R (PKR) and Toll-like receptors 3, 7, and 9 was also measured from cell lysates. RESULTS PBMCs from pregnant women produced significantly less IFN-α (median level, 114.06 pg/mL [range, 51.48-394.9]) and IFN-λ (median level, 30.65 pg/mL [range, 0-260]), compared with PBMCs from nonpregnant women (median level, 800.38 pg/mL [range, 259-1458] and 479.87 pg/mL [257.1-1113], respectively; P < .01). PKR expression was also significantly reduced in PBMCs from pregnant women (P < .05). Vaccination significantly improved innate and adaptive immunity in pregnancy (P < .01). CONCLUSION PBMCs from nonvaccinated pregnant women have attenuated antiviral immunity following H1N1/09 stimulation, but vaccination improves this response. These novel findings help improve understanding of the increased susceptibility and disease severity to influenza virus infection during pregnancy and the importance of influenza vaccination.

Background Acute respiratory tract infections are common ailments to all individuals and the human rhinoviruses (HRVs) cause most of these infections. Pregnant women have increased susceptibility and disease severity to viral infections like influenza and HRVs, as do asthmatics. Successful pregnancy requires immunological modulation to permit fetal tolerance. Objectives To determine whether pregnant women have reduced innate antiviral interferon (IFN) responses to HRV infection compared with non-pregnant women. Methods An in vitro culture system was used, where peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of 54 women, including 10 stable asthmatics who were pregnant and 10 who were not pregnant, 10 non-asthmatic women who were pregnant, 10 who were ≥6 months post partum and 10 who were not pregnant. Samples were also collected from four exacerbating pregnant asthmatics. PBMCs were cultured with HRV43 and HRV1B. The antiviral proteins IFNα and IFNλ were measured from culture supernatants by ELISA. Results Compared with healthy non-pregnant women, pregnant women had significantly reduced innate IFN responses to HRV infection (p Conclusions Reduced antiviral IFNs during pregnancy and asthma provide an important mechanism for increased susceptibility, morbidity and mortality in pregnant women with respiratory viral infection.

Rhinovirus (RV) infection is an important trigger of acute asthma and COPD. Study objectives; were to characterise the response of PBMCs and CD8 lymphocytes when exposed to RV infected bronchial epithelial cells. Methods; Human Calu3 cells were used as a model for bronchial epithelial cells and infected with RV-43 and RV-1B. PBMCs were obtained from healthy individuals and separated by Ficoll-Paque centrifugation. CD8 lymphocytes were identified as CD3+, CD8+ by flow cytometry. PBMCs were exposed to infected Calu3 cells, cells exposed to UV inactive RV, PHA and TLR3 agonist PolyI:C. Response was measured by ELISA for release of interferon(IFN)-γ and TNF-α. CD8 activation with expression of perforin or proliferation measured by carboxyfluorescein succinimidyl ester assay. Results: Exposure of PBMCs to Calu3 cells infected with both RV led to significant release of IFN-γ and TNF-α, smaller release was seen in response to UV inactive RV. Exposure to PolyI:C also led to a similar release. CD8+ cells were found to be the primary source of IFN-γ release. CD8+ cells did not show an increase in perforin expression or evidence of proliferation. Conclusions; exposure of PBMCs and CD8+ cells to an RV infected bronchial epithelium alone results in an innate immune response mediated by TLR3 without evidence of a CD8 adaptive immune response.