Development of solitary chemosensory cells in the distal lung after severe influenza injury

Am J Physiol Lung Cell Mol Physiol. 2019 Jun 1;316(6):L1141-L1149. doi: 10.1152/ajplung.00032.2019. Epub 2019 Mar 25.


H1N1 influenza virus infection induces dramatic and permanent alveolar remodeling mediated by p63+ progenitor cell expansion in both mice and some patients with acute respiratory distress syndrome. This persistent lung epithelial dysplasia is accompanied by chronic inflammation, but the driver(s) of this pathology are unknown. This work identified de novo appearance of solitary chemosensory cells (SCCs), as defined by the tuft cell marker doublecortin-like kinase 1, in post-influenza lungs, arising in close proximity with the dysplastic epithelium, whereas uninjured lungs are devoid of SCCs. Interestingly, fate mapping demonstrated that these cells are derived from p63-expressing lineage-negative progenitors, the same cell of origin as the dysplastic epithelium. Direct activation of SCCs with denatonium + succinate increased plasma extravasation specifically in post-influenza virus-injured lungs. Thus we demonstrate the previously unrecognized development and activity of SCCs in the lung following influenza virus infection, implicating SCCs as a central feature of dysplastic remodeling.

Keywords: chemosensory; inflammation; influenza; progenitor; tuft.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Lung Injury / pathology*
  • Acute Lung Injury / virology
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Cells, Cultured
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Inflammation / pathology
  • Influenza A Virus, H1N1 Subtype / metabolism*
  • Influenza, Human / pathology*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lung / pathology
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / pathology
  • Protein-Serine-Threonine Kinases / metabolism
  • Respiratory Distress Syndrome / pathology*
  • Respiratory Mucosa / pathology*
  • Respiratory Mucosa / virology


  • CKAP4 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • DCLK1 protein, human
  • Protein-Serine-Threonine Kinases