Female sex hormones change the antiviral response of the bronchial epithelium in women with severe asthma

Rhinoviruses (RVs), infecting respiratory epithelial cells, frequently trigger asthma exacerbations. RV replication occurs in close proximity to lipid droplets, cellular organelles that store lipids and regulate many cellular functions. Female sex hormone levels are linked to the asthma exacerbation risk and alter cellular processes, e.g. fatty acid metabolism. However, their effect on the antiviral response of bronchial epithelial cells (BECs) is unknown. Our aim is to identify a mechanistic link between female sex hormones and the antiviral response of BECs with a focus on lipid droplets. BECs from female patients with severe asthma and non-asthma controls were exposed to β-estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH) or Luteinising Hormone (LH) followed by RV16 infection. Physical and immunological barrier properties and RV16 replication were assessed. The inflammatory response during RV16 infection and viral replication was mainly affected by P4 or LH, with P4 increasing viral replication in severe asthma but not in non-asthma controls. On the transcriptomic level, P4 or LH dependent changes in the antiviral response were identified using RNAseq. Lipid droplets were isolated and sex hormone induced changes in the fatty acid composition during RV16 infection determined by gas chromatography. Our data show that female sex hormones influence the antiviral response of BECs. Importantly, we identified differences in the response of BECs derived from women with severe asthma compared to non-asthma controls. This enhances our understanding of RV infections in women with asthma and identifies a mechanistic link to the fatty acid composition of lipid droplets.