Poster Presentation Lorne Infection and Immunity 2023

Tuft cells regulate inflammation in the lung during influenza A virus infection (#162)

Jacqueline Marshall 1 , Philip Hansbro 1 , Gang Liu 1 , Gabrielle Belz 2 , Scott Byrne 3 , Michael Buchert 4 , Elinor Hortle 1 , Ridhima Wadhwa 1 , Shatarupa Das 1 , Angelica Katsifis 1 , Piyush Jha 1
  1. Centre for Inflammation, Centenary Institute, UTS, Sydney, NSW, Australia
  2. The University of Queensland Diamantina Institute, Woolloongabba, Brisbane, Queensland, Australia
  3. Westmead Institute for Medical Research, Centre for Immunology and Allergy Research, Sydney, New South Wales, Australia
  4. Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University, Melbourne, Australia

Tuft cells are rare, solitary, specialised epithelial cells found in most mucosal tissues. They have important roles in initiating and propagating immune responses in the gastrointestinal tract. However, the role of tuft cells in the respiratory tract has not been extensively studied, and their potential roles in respiratory inflammation during lung infection remains unclear. In this study, we investigate the role of airway tuft cells during inflammation in a mouse model of influenza A virus (IAV) infection. Double cortin-like kinase 1 (DCLK1) is a widely used marker of murine tuft cells. We used a tamoxifen inducible DCLK1 deleter mouse to deplete DCLK1+ cells from C57BL/6 mice, then infected them with 33 p.f.u. of A/PR8 H1N1 IAV or sham. At day 7 post infection, DCLK1 deleter mice had significantly reduced numbers of total leukocytes in bronchoalveolar lavage fluid (BALF) compared to WT controls in cytospins. IAV infected DCLK1 deleter mice had no changes in neutrophil numbers in the lung tissues but significantly increased total numbers of neutrophils in the blood compared to WT controls by flow cytometry. Infected deleter mice showed an increase of IFN-Y and IL-6 and a decrease of IL-10 in BALF, and increased mRNA expression of IL-1b, IL-6, CXCL-1 and IFN-Y in the lung tissue after 7 days post infection compared to WT controls. Our data indicate that airway tuft cells contribute to inflammation in the lung during flu infection.