Image of the mouse lung showing endothelial cells lining the blood vessels in red and nuclei of the cells in blue. Air spaces are the dark areas of the image. The cyan and yellow marks show AHR and one of its target genes (Cyp1a1) being expressed in lung endothelial cells. Credit: Jack Major, Nature (2023).
Key points:
- Molecules in cruciferous vegetables activate a protein found at barrier sites like the gut and the lung.
- In mice, when the protein was overactivated, less blood entered the lung spaces.
- Next, the researchers want to examine the impact of respiratory viruses on the protein.
Researchers at the Francis Crick Institute have found that molecules in vegetables like broccoli or cauliflower help to maintain a healthy barrier in the lung and ease infection.
For the study, published in Nature, researchers conducted a series of experiments in mice to show how aryl hydrocarbon receptor (AHR)—a protein found at barrier sites like the gut and lung—functions. When mice were infected with the flu virus, blood was found in the airspaces in the lungs, as it had leaked across the damaged barrier. The researchers then showed that AHR was able to prevent the barrier from becoming leaky: when AHR was overactivated they observed less blood in the lung spaces.
They also found that mice with enhanced AHR activity didn’t lose as much weight when infected with flu, and were able to better fight off a bacterial infection on top of the original virus.
When AHR was prevented from being expressed in the lung endothelial cells of infected mice, more blood and immune cells were seen in the air spaces, showing greater damage to the barrier.
The researchers also showed that flu infection causes a decrease in protective lung AHR activity, but only in mice fed AHR ligands in their diet before the illness. These findings link food consumption to AHR activity and outcome in viral infection—infected mice didn’t eat as much food when ill, so their intake of AHR ligands was reduced and the AHR system was less active, leading to more lung damage.
Despite the infection-driven reduction of AHR activity, it was beneficial for mice to be on an AHR ligand-rich diet. These mice had better barrier integrity and less lung damage during infection than mice on the control diet. The scientists say these results indicate that AHR has a protective effect on the lung barrier, which is impacted by infection, but can be improved by the right diet.
“What we’ve identified is a gut-lung axis—linking diet to protection against lung infection via endothelial cells,” said first author Jack Major, visiting scientist at Crick. “We looked at flu in this research, but other research has shown that COVID-19 may also reduce AHR activity in the lung. It will be interesting to investigate the impact of other respiratory viruses on AHR, and also whether different molecules in our diet use other pathways than AHR to affect lung function via endothelial cells.”