Harvard study claims humans can help fight diseases simply by breathing

By Mark Waghorn via SWNS

Humans can fight off viruses simply by breathing, according to new research.

It generates immune responses that kill invading pathogens, say scientists.

In experiments, a 'lung chip' that mimics the mechanical forces killed flu bugs.

The discovery could lead to the development of better medications for respiratory diseases - including COVID-19.

Co-first author Dr. Haiqing Bai, of Harvard University, Boston, said: "This research demonstrates the importance of breathing motions for human lung function, including immune responses to infection.

"It shows our Human Alveolus Chip can be used to model these responses in the deep portions of the lung, where infections are often more severe and lead to hospitalization and death."

The alveoli are where the lungs and the blood exchange oxygen and carbon dioxide during the process of breathing in and out.

Dr. Bai said: "This model can also be used for preclinical drug testing to ensure candidate drugs actually reduce infection and inflammation in functional human lung tissue."

The average person will take more than 600 million breaths over the course of their life. They stretch and relax the lungs with each inhale and exhale, respectively.

The mere motions influence their development and vital functions. The study in Nature Communications now shows their role in combating infection.

It also identified drugs that reduced the production of inflammatory proteins called cytokines - one of which is licensed to treat Covid.

The coronavirus can generate a "cytokine storm" that can have deadly consequences - leading to organ failure.

The lung chip will shed fresh light on how lung tissues react to respiratory viruses that have pandemic potential and test potential treatments.

Dr. Bai and colleagues lined the two parallel microfluidic channels with different types of living human cells.

They included alveolar lung cells in the upper channel and lung blood vessel cells in the lower channel.

It recreated the interface between human air sacs and their blood-transporting capillaries.

The channel lined by alveolar cells was filled with air while the blood vessel channel was perfused with a flowing culture medium containing nutrients that are normally delivered via the blood.

The channels were separated by a porous membrane that allowed molecules to flow between them.

The team infected these 'breathing' Alveolus Chips with H3N2 influenza by introducing the virus into the air channel.

They observed the development of several known hallmarks of infection, including the breakdown of junctions between cells, a 25% increase in cell death and the initiation of cellular repair programs.

Infection also led to much higher levels of multiple inflammatory cytokines in the blood vessel channel.

In addition, the blood vessel cells of infected chips expressed higher levels of immune cells.

The results confirmed that the Alveolus Chip was mounting an immune response against H3N2 that recapitulated what happens in the lung of human patients infected with the flu virus.

To their surprise, chips exposed to breathing motions ​​had 50% less viral mRNA in their alveolar channels and a significant reduction in inflammatory cytokine levels compared to static chips.

Genetic analysis revealed the mechanical strain had activated molecular pathways related to immune defense and multiple antiviral genes, and these activations were reversed when the cyclical stretching was stopped.

Co-first author Professor Longlong Si, now at the Shenzhen Institute of Advanced Technology, China, said: "This was our most unexpected finding - that mechanical stresses alone can generate an innate immune response in the lung."

A higher strain caused an increase in innate immune response genes and processes, including several inflammatory cytokines.

Prof Si said: "Because the higher strain level resulted in greater cytokine production, it might explain why patients with lung conditions like COPD suffer from chronic inflammation, and why patients who are put on high-volume ventilators sometimes experience ventilator-induced lung injury.

The team is exploring the incorporation of additional cell types such as macrophages into the chips to increase their complexity and model more biological processes, such as adaptive immunity.

They are also using their existing model to study the efficacy of new compounds, drugs, and biologics against flu, COVID-19 and other diseases.