Fighting viruses is as easy as breathing on a human lung chip

Amazing stuff! What is all the RAGE about? Hint: Receptor for advanced glycation end products. 😄

Or how to "Creating a flu-on-a-chip".

"The average person will take more than 600 million breaths over the course of their life. ... Now, new research ... has revealed that this constant pattern of stretching and relaxing [of the lungs] does even more – it generates immune responses against invading viruses. ...
Using a Human Lung Chip that replicates the structures and functions of the lung air sac, or “alveolus,” the research team discovered that applying mechanical forces that mimic breathing motions suppresses influenza virus replication by activating protective innate immune responses. They also identified several drugs that reduced the production of inflammatory cytokines in infected Alveolus Chips, which could be useful in treating excessive inflammation in the lung. ...
Human Organ Chips were developed to address this problem, and have been shown to faithfully replicate the functions of many different human organs in the lab, including the lung. ... since 2017, ... researchers have been working on replicating various diseases in Lung Airway and Alveolus Chips to study how lung tissues react to respiratory viruses that have pandemic potential and test potential treatments. ..."

From the 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."

Fighting viruses is as easy as breathing Human Lung Chip reveals the effects of breathing motions on lung immune responses and leads to repurposing of potential therapeutics for respiratory diseases, including COVID-19

Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip (open access)