TY - JOUR T1 - Crucial role of iron metabolism in determining outcomes of influenza A virus infection and disease JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2022.877 VL - 60 IS - suppl 66 SP - 877 AU - J Mayall AU - A Pillar AU - K Daly AU - A Brown AU - A Essilfie AU - H Gomez AU - R Kim AU - K Nichol AU - C Donovan AU - G Anderson AU - D Frazer AU - E Milward AU - P Hansbro AU - D Reid AU - A Hsu AU - P Wark AU - J Horvat Y1 - 2022/09/04 UR - http://erj.ersjournals.com/content/60/suppl_66/877.abstract N2 - Introduction: The interplay between iron, infection and immunity is important in the pathogenesis of bacterial infections, however, the relationship between respiratory viral infections and iron metabolism is largely unknown. Here we investigated the relationship between iron levels and metabolism and the pathogenesis of influenza A virus (IAV) infections.Methods: Bronchial epithelial cells were cultured with ferric ammonium citrate (FAC) prior to infection with IAV (H1N1) to assess the effects of increased iron in human airways. BALB/c mice were intranasally infected with IAV (PR8/H1N1) and regulation of iron related genes in lung tissue assessed. Groups of mice were placed on a high iron or control chow diet for 8 weeks prior to infection or were treated with anti-transferrin receptor (TFR)1 antibody during infection to assess the effects of increased iron levels and depletion of TFR1-mediated cellular iron uptake on infection and disease.Results: IAV infection reduces the expression of genes for iron uptake proteins, TFR1 and divalent metal transporter (DMT)1, in human cells and murine lung tissue and decreases expression of genes for iron storage proteins, ferritin light (FTL) and heavy (FTH) chains, in the murine lung. Increasing iron levels in human bronchial epithelial cells increases IAV titre from 24hrs post infection. Increased iron levels in the murine lung increase inflammation and airflow obstruction, while depletion of TFR1+ cells decreases inflammation and airflow obstruction during IAV infection.Conclusions: IAV infections alter iron metabolism in the airways and lungs. Iron metabolism plays an important role in IAV-induced disease and may be targeted therapeutically.FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 877.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -