Correlation of Chest CT and RT-PCR Testing for Coronavirus ...

Molecules In Vegetables Can Help To Ease Lung Infection

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.

The AHR -- aryl hydrocarbon receptor -- is a protein found at barrier sites like the gut and the lung. Natural molecules in cruciferous vegetables -- for example, kale, cauliflower, broccoli, or cabbage -- are dietary 'ligands' for AHR, which means, once eaten, they activate AHR to target a number of genes. Some of the genes targeted switch off the AHR system, allowing it to self-regulate.

The effect of AHR on immune cells is well understood, but this research, published today in Nature, now shows that AHR is also highly active in endothelial cells lining blood vessels in the lung.

The lung barrier between the body and the air outside is only made up of two layers, one of endothelial cells and one of epithelial cells, because it needs to allow oxygen to enter. But the barrier also has to be kept strong against pollution or viruses and bacteria.

The researchers conducted a series of experiments in mice to show how AHR impacts lung barriers. 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. 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.

Andreas Wack, Group Leader of the Immunoregulation Laboratory at the Crick, said, "Until recently, we've mainly looked at barrier protection through the lens of immune cells. Now we've shown that AHR is important for maintaining a strong barrier in the lungs through the endothelial cell layer, which is disrupted during infection.

"People may be less likely to maintain a good diet when they're ill, so aren't taking in the molecules from vegetables which make this system work. It's a good idea to eat lots of cruciferous vegetables anyway, but this shows it's even more important to continue eating them when you're ill!"

Jack Major, former PhD student in the Wack lab and now visiting scientist at the Crick and first author, said: "What we've identified is a gut-lung axis -- linking diet to protection against lung infection via endothelial cells.

"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."

Researchers believe AHR may be important in endothelial cells in other barrier organs. A team at MRC and Imperial have reported in Nature* today that dietary factors activate AHR in the gut endothelial cells, preventing excessive cell reproduction and inflammation. Similar to the process in the lung, the authors show gut endothelial AHR is important in protection against gut infection. This provides another link between the diet and the state of the gut endothelium, an important contributor to gut health. First author Ben Wiggins has now joined the Immunoregulation Laboratory at the Crick to work with Andreas Wack.

Study Among First To Show Drugs Targeting The Lung, Rather Than Bacteria, May Prevent Staph Infection In Flu Patients

Influenza infection (flu) is a major cause of death around the world, especially during years of flu pandemics. People who die of the flu often have a secondary lung infection with Staphylococcus aureus (staph) bacteria that starts a few days after flu infection begins. In new research, a team from Mount Sinai studied how the flu paves the way for staph infection in the lungs. Using mouse models, the researchers found that healthy lungs secrete liquid into their air sacs that prevents a staph infection. The flu blocks this liquid secretion by inhibiting a protein called CFTR, making it possible for staph that are inhaled into the air sacs to stick to the air sac walls, initiate infection, and damage the lungs. Treatment with a CFTR-activating drug, such as ivacaftor, restores liquid secretion in air sacs of the flu-infected lungs and restores the air sacs' natural protection against staph infection.

The study is published in the Journal of Clinical Investigation.

The researchers applied a method to examine live air sacs of intact, perfused mouse lungs. Mice were untreated or intranasally instilled with the flu at 24 hours before lung imaging. The researchers used a pink dye to view air sac walls and a yellow solution to visualize the air sac liquid. In untreated lungs, loss of fluorescence of the yellow solution over time indicated that the solution was diluted by non-fluorescent liquid, which was secreted into the air sacs by cells that line the air sac walls. By contrast, in lungs infected with the flu, the yellow fluorescence was not lost, signaling that air sac walls failed to secrete liquid. Treatment of the air sac walls of flu-infected lungs with the CFTR-activating drug ivacaftor restarted the liquid secretion. Follow-up studies in mice co-infected with flu and staph showed that the loss of liquid secretion caused inhaled staph to stick to air sac walls, leading to staph infection, lung injury, and death.

The research uncovers how lung air sacs normally protect themselves against staph lung infection and reveals how flu disrupts that protection to make it easy for staph to cause secondary lung infection. The study also explores the possibility of giving ivacaftor to people with flu infection to prevent secondary staph infection, a deadly complication of the flu.

Researchers say these findings support a potential pathway for clinical trials that test whether ivacaftor can prevent secondary staph infection in people with the flu, which is highly feasible since the medication is already in clinical use for both children and adults and has a good record of safety and tolerability.

Speaking about the research, Mount Sinai's Jaime Hook, MD said, "The combination of flu and staph infections in the lungs is deadly, particularly in young children and older people. Antibiotics don't always resolve the staph infection because they might be started after the infection is already severe and it's too late to treat it, or because the antibiotics don't work if the bacteria are antibiotic-resistant. Our work shows, for the first time, how drugs that target the lung—rather than the bacteria—might treat staph infection in flu-infected lungs. We think that drugs that activate the CFTR protein, like ivacaftor, rescue a critical lung defense mechanism in flu-infected lungs to restore the lung's natural protection against staph infection. In this way, giving CFTR activator drugs to people with the flu who are at risk for a secondary staph infection might prevent staph infection from initiating, thereby preventing death from flu-staph coinfection."

Study authors include Jaime Hook, MD, Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine), and Microbiology, at the Icahn School of Medicine at Mount Sinai; Stephanie Tang, Ph.D. Candidate in the Graduate School of Biomedical Sciences at Icahn Mount Sinai; and other co-authors. Researchers from Yale University School of Medicine and the Vagelos College of Physicians and Surgeons at Columbia University also contributed to the study.

More information: Stephanie Tang et al, Rescue of alveolar wall liquid secretion blocks fatal lung injury by influenza-staphylococcal coinfection, Journal of Clinical Investigation (2023). DOI: 10.1172/JCI163402

Citation: Study among first to show drugs targeting the lung, rather than bacteria, may prevent staph infection in flu patients (2023, August 15) retrieved 27 August 2023 from https://medicalxpress.Com/news/2023-08-drugs-lung-bacteria-staph-infection.Html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Lung Disease News

Apr. 21, 2023 — Storing donor lungs for transplant at 10 degrees Celsius markedly increases the length of time the organ can live outside the body according to new ...

Mar. 28, 2023 — Researchers develop a 3D cell culture system to test how inhibiting fibroblast activities can help treat lung cancer. To simulate the tumor microenvironment and mimic real tissues, the team ...

Mar. 17, 2023 — A new study has revealed FDA-approved trametinib and entinostat (which is currently in clinical trials) can be given in tandem to produce fewer and smaller tumors in mice with LKB1-mutated non-small ...

Mar. 15, 2023 — A new study represents a first step towards generating highly detailed 3-dimensional maps of lung tumors using genetically engineered mouse ...

Mar. 13, 2023 — Scientists have discovered why breast cancer cells that have spread to the lungs may 'wake up' following years of sleep -- forming incurable secondary tumors. Their research reveals the ...

Mar. 10, 2023 — One in 10 adults suffer from the debilitating effects of chronic obstructive pulmonary disease (COPD). Research around a new breathing device developed by pulmonologists offers promise for improving ...

Mar. 9, 2023 — Congenital diaphragmatic hernia is one of the deadliest birth defects. To better understand and treat this condition in the future, researchers designed a new cell model in the laboratory and tested ...

Mar. 8, 2023 — Contracting a lower respiratory tract infection in early childhood is associated with a higher risk of dying from respiratory disease as an adult, according to new ...

Feb. 27, 2023 — New research reveals how the relationship between nerves and immune cells in the lungs can contribute to the development of allergic ...

Feb. 23, 2023 — As air pollution in Stockholm has decreased, so has the lung capacity of children and adolescents has improved, a new study reports. The researchers consider the results important, since the lung ...

Feb. 22, 2023 — A new study uncovers how a protein, APOBEC3B, could protects cells against many different types of RNA viruses like respiratory syncytial virus (RSV), SARS-CoV2, influenza virus, poliovirus and ...

Feb. 8, 2023 — A new study reveals how resistance to bacteraemic pneumonia is provided by a unique subset of lung T regulatory ...

Feb. 1, 2023 — New data from a clinical trial shows improved rates of survival and reduced risk of recurrence in patients taking osimertinib, a targeted therapy for non-small cell lung cancer ...

Jan. 19, 2023 — Researchers demonstrate that a bacteria can be modified to act as 'living medicine' in the lung. The treatment significantly reduced acute lung infections in mice and doubled their survival ...

Jan. 12, 2023 — More than 2,500 genes exhibit significant sex differences in expression in mouse alveolar type II cells (AT2s), important for keeping the lungs functioning, potentially explaining sex biases in the ...

Jan. 9, 2023 — A new study found that deleting a gene called KMT2D caused normal (basal) lung cells grown in complex cultures called organoids to transform into lung squamous carcinoma (LUSC) ...

Jan. 5, 2023 — A new method of donor-lung distribution is projected to decrease the number of candidate deaths who are on the waitlist for lung transplant, according to a new ...

Jan. 4, 2023 — A research team has shown that Sarunashi juice and its constituting component isoquercetin help prevent and reduce lung cancer in laboratory ...

Dec. 28, 2022 — Researchers have found that antigen-specific killer T cells (CD8+ T cells) rapidly expand in the lungs when primed by antigen-presenting lung-resident alveolar macrophages (AMs). This interaction ...

Dec. 26, 2022 — Researchers report that they have developed a new experimental pipeline to combine bacterial therapy with current cancer drugs. Their study, which explores resistance to bacterial therapy at the ...

Friday, April 21, 2023

Tuesday, March 28, 2023

Friday, March 17, 2023

Wednesday, March 15, 2023

Monday, March 13, 2023

Friday, March 10, 2023

Thursday, March 9, 2023

Wednesday, March 8, 2023

Monday, February 27, 2023

Thursday, February 23, 2023

Wednesday, February 22, 2023

Wednesday, February 8, 2023

Wednesday, February 1, 2023

Thursday, January 19, 2023

Thursday, January 12, 2023

Monday, January 9, 2023

Thursday, January 5, 2023

Wednesday, January 4, 2023

Wednesday, December 28, 2022

Monday, December 26, 2022

Thursday, December 22, 2022

Wednesday, December 21, 2022

Tuesday, December 6, 2022

Monday, December 5, 2022

Friday, December 2, 2022

Thursday, December 1, 2022

Wednesday, November 30, 2022

Tuesday, November 29, 2022

Tuesday, November 22, 2022

Monday, November 21, 2022

Thursday, November 17, 2022

Wednesday, November 16, 2022

Tuesday, November 15, 2022

Tuesday, November 8, 2022

Thursday, November 3, 2022

Wednesday, November 2, 2022

Wednesday, October 26, 2022

Tuesday, October 25, 2022

Monday, October 17, 2022

Monday, October 10, 2022

Tuesday, October 4, 2022

Tuesday, September 27, 2022

Friday, September 23, 2022

Thursday, September 22, 2022

Monday, September 19, 2022

Friday, September 16, 2022

Thursday, September 15, 2022

Wednesday, September 14, 2022

Tuesday, September 13, 2022

Thursday, September 8, 2022

Tuesday, September 6, 2022

Monday, September 5, 2022

Friday, September 2, 2022

Thursday, September 1, 2022

Wednesday, August 31, 2022

Thursday, August 25, 2022

Thursday, August 18, 2022

Tuesday, August 9, 2022

Monday, August 8, 2022

Tuesday, August 2, 2022

Monday, August 1, 2022

Thursday, July 28, 2022

Wednesday, July 27, 2022

Tuesday, July 26, 2022

Monday, July 25, 2022

Wednesday, July 20, 2022

Monday, July 18, 2022

Thursday, July 14, 2022

Tuesday, July 5, 2022

Wednesday, June 29, 2022

Thursday, June 23, 2022

Tuesday, June 21, 2022

Tuesday, June 14, 2022

Friday, June 10, 2022

Thursday, June 9, 2022

Friday, June 3, 2022

Thursday, June 2, 2022

Tuesday, May 24, 2022

Wednesday, May 11, 2022

Monday, May 9, 2022

Thursday, May 5, 2022

Wednesday, May 4, 2022

Tuesday, May 3, 2022

Thursday, April 28, 2022

Monday, April 25, 2022

---