Inflammatory and antiviral responses to influenza A virus infection are dysregulated in pregnant mice with allergic airway disease

Background: Influenza A virus (IAV) infections are increased during pregnancy especially with asthma as a comorbidity, leading to asthma exacerbations, secondary bacterial infections, intensive care unit admissions and mortality. Objective: We aimed to define the processes involved in increased susceptibility and severity of IAV infections during pregnancy, especially with asthma Methods: We sensitised mice to house dust mite (HDM), induced pregnancy and challenged with HDM to induce allergic airway disease (AAD). Mid pregnancy, we induced IAV infection. We assessed viral titres, airway inflammation, lung anti-viral responses, mucus hyper-secretion and airway hyper-responsiveness (AHR). Results: During early IAV infection, pregnant mice with AAD had increased mRNA expression of the inflammatory markers Il13 and IL17 and reduced mRNA expression of the neutrophil chemoattractant marker, Kc. These mice had increased mucous hyperplasia and increased AHR. miR155, miR574, miR223, and miR1187 were also reduced during early infection, as was mRNA expression of the anti-viral β-defensins, Bd1, Bd2, and Spd and IFNs, Ifnα, Ifnβ and Ifnλ. During late infection Il17 was still increased as was eosinophil infiltration in the lungs. mRNA expression of Kc was reduced, as was neutrophil infiltration and mRNA expression of the anti-viral markers Ifnβ, Ifnλ, Ifnγ and Ip10, Tlr3, Tlr9, Pkr and Mx1. Mucous hyperplasia was still significantly increased as was AHR. Conclusions and Clinical Relevance: Early phase IAV infection in pregnancy with asthma heightens underlying inflammatory asthmatic phenotype and reduces anti-viral responses.