Mitogenic stimulation accelerates influenza-induced mortality by increasing susceptibility of alveolar type II cells to infection

• DOI: 10.1073/pnas.1621172114
• Publication Date: 2017-08-02T20:52:26Z
• Authors: Nikolaos M. Nikol...; John G. Noel; Lori B. Pitstick; Jason C. Gardner; Yasuaki Uehara; Huixing Wu; Atsushi Saito; Kara E. Lewnard; Huan Liu; Mitchell R. White; Kevan L. Hartshorn; Francis X. McCormack
• Keywords: 0301 basic medicine; Fibroblast Growth Factor 7; 3. Good health; Mice; 03 medical and health sciences; Orthomyxoviridae Infections; Influenza A virus; Mice, Inbred DBA; Alveolar Epithelial Cells; Animals; Female; Disease Susceptibility; Mitogens; Cell Proliferation

Significance Influenza is a recurring global health threat that preferentially targets vulnerable groups such as the very young, the pregnant, the elderly, and the infirm. The spread of influenza A virus (IAV) from the epithelium of the conducting airway to the alveolar epithelium is a pivotal event in the pathogenesis of primary viral pneumonia. Host susceptibility to IAV pneumonia is often attributed to altered immunity, and cell autonomous vulnerability states of the alveolar epithelium, such as proliferative tone, are rarely considered. Here we demonstrate that mitogenic stimulation of alveolar epithelial type II cells renders them susceptible to IAV infection in an mTOR-dependent manner.