Impaired type I and III interferon response to rhinovirus infection during pregnancy and asthma
- 1Centre for Asthma and Respiratory Disease, The University of Newcastle, School of Medicine and Public Health and Hunter Medical Research Institute, Newcastle, New South Wales, Australia
- 2Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton, New South Wales, Australia
- Correspondence to Rebecca Louise Forbes, Department of Respiratory Medicine, Locked Bag 1, Hunter Region Mail, New Lambton, NSW, Australia, 2350;
Contributors PGG, PABW and VEM were responsible for the planning and intellectual input/advice for the article. RLF was responsible for the planning, conduct and reporting of the work described in the article.
- Received 30 January 2011
- Accepted 11 August 2011
- Published Online First 13 September 2011
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<0.02), persisting ≥6 months post partum (p≤0.02). Pregnant asthmatics had significantly reduced IFNλ responses compared with healthy non-pregnant women (p≤0.034), while during current asthma exacerbations a decrease in IFNα (p≤0.023) and IFNλ (p=0.007) was observed. Induction by a TLR7 agonist induced a similar pattern of decreased innate IFNs during pregnancy as observed when HRV was the inducing agent.
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.
Funding The National Health and Medical Research Council of Australia (NHMRC), Australia, and Australian Postgraduate Association (APA) PhD Scholarship, NSW, Australia, grant number 455593 and 455626, to provide financial support required for recruiting, consumables, staff, etc, needed to undertake the research project.
Competing interests None.
Ethics approval Hunter New England Human Research Ethics Committee and the University of Newcastle Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.