Expanded IL-22 producing γδ T cells after neonatal respiratory viral infection are required for lung repair 2241785

Abstract Introduction Human metapneumovirus (HMPV) is a respiratory virus that can lead to lower respiratory tract infection (LRTI), causing 500,000 hospitalizations and 11,000 deaths in children under 5 worldwide annually. Early life viral LRTI leads to persistent abnormalities in lung function and increased risk of asthma development. The lungs continue to develop postnatally via alveolarization for the first few years of life in children and the first 4 weeks in mice. The healing mechanisms in the lung following viral LRTI remain largely unknown. Methods We modeled neonatal HMPV infection with mice at day of life 4-6 compared to adult mice with infection at 6-8 weeks. HMPV infected alveolar epithelial cells 1 day post infection (DPI) with total viral clearance by 7 DPI. Results Neonatal mice saw a robust expansion of γδ T cells at 1 DPI that was not present in adult mice. These γδ T cells expressed high levels of IL-22, a cytokine involved in epithelial protection and repair. γδ T cell deficient mice (e.g. Tcrd-/-) infected as neonates did not produce IL-22 at 1 DPI. At 7 DPI, B6 neonates had markers of lung repair as evidenced by clusters of Krt5+ cells in alveolar spaces. Krt5 was significantly decreased in Tcrd-/- mice at the same timepoint. Neonatal Tcrd-/- mice presented with increased pathology in the alveolar spaces 21 DPI compared to B6 mice. Conclusion These data show that γδ T cells upon neonatal infection are critical to initiate epithelial repair pathways that mediate lung damage caused by viral pathogens. Funding Source AAAAI Foundation Faculty Development Award K08AI182486, National Institute of Allergy and Infectious Diseases Topic Categories Mucosal and Regional Immunology (MUC)