@article{661,
  keywords = {Antimicrobial responses, Innate immunity, Tissue engineering, Viral infection},
  author = {Haiqing Bai and Longlong Si and Amanda Jiang and Chaitra Belgur and Yunhao Zhai and Roberto Plebani and Crystal Yuri Oh and Melissa Rodas and Aditya Patil and Atiq Nurani and Sarah E. Gilpin and Rani K. Powers and Girija Goyal and Rachelle Prantil-Baun and Donald E. Ingber},
  title = {Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip},
  abstract = {Mechanical breathing motions have a fundamental function in lung development and disease, but little is known about how they contribute to host innate immunity. Here we use a human lung alveolus chip that experiences cyclic breathing-like deformations to investigate whether physical forces influence innate immune responses to viral infection. Influenza H3N2 infection of mechanically active chips induces a cascade of host responses including increased lung permeability, apoptosis, cell regeneration, cytokines production, and recruitment of circulating immune cells. Comparison with static chips reveals that breathing motions suppress viral replication by activating protective innate immune responses in epithelial and endothelial cells, which are mediated in part through activation of the mechanosensitive ion channel TRPV4 and signaling via receptor for advanced glycation end products (RAGE). RAGE inhibitors suppress cytokines induction, while TRPV4 inhibition attenuates both inflammation and viral burden, in infected chips with breathing motions. Therefore, TRPV4 and RAGE may serve as new targets for therapeutic intervention in patients infected with influenza and other potential pandemic viruses that cause life-threatening lung inflammation.},
  year = {2022},
  journal = {Nature Communications},
  volume = {13},
  pages = {1928},
  month = {2022-04-08},
  issn = {2041-1723},
  url = {https://www.nature.com/articles/s41467-022-29562-4},
  doi = {10.1038/s41467-022-29562-4},
  language = {en},
}