Immune Dysfunction in Ataxia Telangiectasia Mutated Lung Disease
Reactive oxygen species produced during hyperoxia damage DNA, resulting in the activation of the ataxia telangiectasia mutated (ATM) kinase that promotes survival of oxidized cells. Individuals with mutations in ATM are sensitive to oxidative stress, but frequently succumb to recurrent respiratory infections through poorly understood mechanisms. Although overt lung disease is not seen in mice lacking ATM, we discovered that they fail to develop sterilizing immunity to influenza A virus or to properly regenerate the infected airway epithelium. Current studies are designed to understand how ATM is required for development of immune memory and airway epithelial regeneration following influenza A virus infections.