Cystic fibrosis (CF) is a chronic condition that causes the build-up of mucus in the lungs, airways and digestive system, which often leads to infections. The new research finds that the macrophages — a white blood cell involved in the immune system — in CF patients lack the zinc levels necessary to kill infection-causing bacteria.
“One way that macrophages destroy bacteria is by poisoning them with toxic levels of metals such as zinc,” says professor Matt Sweet of the Institute for Molecular Bioscience at the University of Queensland, Australia, one of the authors of the paper.
“We discovered that the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel is crucial to the zinc pathway, and because it doesn’t work properly in people with CF, it may partly explain why they’re more susceptible to bacterial infections.” Importantly, the study identifies a zinc transport protein that facilitated the macrophages’ ability to kill bacteria despite the CFTR protein not working.
23 Feb 2024 — Cystic fibrosis (CF) is a chronic condition that causes the build-up of mucus in the lungs, airways and digestive system, which often leads to infections. The new research finds that the macrophages — a white blood cell involved in the immune system — in CF patients lack the zinc levels necessary to kill infection-causing bacteria.
“One way that macrophages destroy bacteria is by poisoning them with toxic levels of metals such as zinc,” says professor Matt Sweet of the Institute for Molecular Bioscience at the University of Queensland, Australia, one of the authors of the paper.
“We discovered that the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel is crucial to the zinc pathway, and because it doesn’t work properly in people with CF, it may partly explain why they’re more susceptible to bacterial infections.”
Importantly, the study identifies a zinc transport protein that facilitated the macrophages’ ability to kill bacteria despite the CFTR protein not working.
Zinc transport protein
The research paper published in PNAS shows that CFTR is needed for the macrophage zinc toxicity antibacterial response. Manipulating zinc availability can restore bacterial killing in CFTR-defective macrophages. Zinc supplementation can restore the bacterial killing capabilities of CF human macrophages responding to the bacteria Pseudomonas aeruginosa in an in vitro macrophage model.
“Our goal now is to deliver this zinc transport protein to macrophages in people with CF with the expectation that it would reactivate their immune response and reduce infections,” Sweet comments.
“People with CF have a hyper-inflammatory state in their airways and are very susceptible to bacterial infections, but frequent treatment with antibiotics can often lead to antibiotic-resistant infections,” adds professor Peter Sly, a pediatric respiratory physician at the University of Queensland Child Health Research Centre and key collaborator on the project.
“Current treatments can restore many aspects of CFTR function, but they don’t resolve or prevent lung infections, so there is a need to restore immune functions.” Currently, there are 3,600 CF patients in Australia, and their average life span is reduced to 47 years.
Nutrition for lung health
The abnormal activity of cathepsin — enzymes that hydrolyze peptide bonds in proteins — has also been found to play a role in CF, with experts suggesting that it may be stabilized through the cysteine proteases found in the Sweet Annie herb (Artemisia annua).
Extracts from the yellow-green microalgae strain Trachydiscus minutus have been shown to significantly inhibit elastase, which has anti-aging benefits and a positive effect on the health of CF patients. Excessive elastase activity has been reported to cause tissue damage in many clinical lung conditions.
Research has also linked omega-3 intake with improved health, especially among people living with the lung condition pulmonary fibrosis.
By Milana Nikolova
Source: NutritionInsight