Nat Immunol . β-Glucan reprograms neutrophils to promote disease tolerance against influenza A virus

[tetano]

Nat Immunol


. 2025 Jan 8.
doi: 10.1038/s41590-024-02041-2. Online ahead of print. β-Glucan reprograms neutrophils to promote disease tolerance against influenza A virus

Nargis Khan[SUP] #[/SUP][SUP] 1 2 [/SUP], Kim A Tran[SUP] #[/SUP][SUP] 3 [/SUP], Raphael Chevre[SUP] 4 [/SUP], Veronica Locher[SUP] 5 [/SUP], Mathis Richter[SUP] 4 [/SUP], Sarah Sun[SUP] 6 [/SUP], Mina Sadeghi[SUP] 3 [/SUP], Erwan Pernet[SUP] 3 [/SUP], Andrea Herrero-Cervera[SUP] 4 [/SUP], Alexandre Grant[SUP] 3 [/SUP], Ahmed Saif[SUP] 3 [/SUP], Jeffrey Downey[SUP] 3 [/SUP], Eva Kaufmann[SUP] 3 7 [/SUP], Shabaana Abdul Khader[SUP] 8 [/SUP], Philippe Joubert[SUP] 9 [/SUP], Luis B Barreiro[SUP] 5 6 [/SUP], Bryan G Yipp[SUP] 10 [/SUP], Oliver Soehnlein[SUP] 4 [/SUP], Maziar Divangahi[SUP] 11 [/SUP]



Affiliations

• PMID: 39779870
• DOI: 10.1038/s41590-024-02041-2

Abstract

Disease tolerance is an evolutionarily conserved host defense strategy that preserves tissue integrity and physiology without affecting pathogen load. Unlike host resistance, the mechanisms underlying disease tolerance remain poorly understood. In the present study, we investigated whether an adjuvant (β-glucan) can reprogram innate immunity to provide protection against influenza A virus (IAV) infection. β-Glucan treatment reduces the morbidity and mortality against IAV infection, independent of host resistance. The enhanced survival is the result of increased recruitment of neutrophils via RoRγt[SUP]+[/SUP] T cells in the lung tissue. β-Glucan treatment promotes granulopoiesis in a type 1 interferon-dependent manner that leads to the generation of a unique subset of immature neutrophils utilizing a mitochondrial oxidative metabolism and producing interleukin-10. Collectively, our data indicate that β-glucan reprograms hematopoietic stem cells to generate neutrophils with a new 'regulatory' function, which is required for promoting disease tolerance and maintaining lung tissue integrity against viral infection.


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[Pathfinder]

New discovery could help protect against influenza

Preclinical trial uncovers how beta-glucan, found in all fungi, can ‘reprogram’ immune cells to prevent lung inflammation

SOURCE: McGill University
February 17, 2025

A component found in all fungi may provide a shield against flu-related lung damage, according to a new study.

A team of scientists led by Maziar Divangahi, Senior Scientist at the Research Institute of the McGill University Health Centre and a Professor in McGill’s Faculty of Medicine and Health Sciences, demonstrated that beta-glucan, administered to mice before their exposure to influenza, can reduce lung damage, improve lung function and lower the risk of illness and death.

(Left), Maziar Divangahi, Nargis Khan and Jeffrey Downey, (Centre) Kim Tran and Prof. Divangahi.

Beta-glucan is found in all fungi, including mushrooms and yeast, as well as grains like oats and barley. The scientists discovered that a unique structure of this component can boost defences against pathogens.

While most research focuses on stopping the virus from replicating, this study explored how to regulate the body’s immunity to infection, a concept known as “disease tolerance.” The researchers discovered that beta-glucan significantly enhanced flu survival rates by modulating immune responses and preventing severe lung inflammation, a common cause of fatality.

These results, published in Nature Immunology, highlight beta-glucan as a promising therapy for influenza and other emerging viral pathogens, said the scientists, adding future research will explore whether the findings can be applied to humans.

“It is remarkable how beta-glucan can reprogram certain immune cells, such as neutrophils, to control excessive inflammation in the lung,” said first author Nargis Khan, who conducted this research as a postdoctoral fellow with Prof. Divangahi and is now an Assistant Professor at the University of Calgary.

“Neutrophils are traditionally known for causing inflammation, but beta-glucan has the ability to shift their role to reduce it,” added co-first author Kim Tran, who recently completed her PhD in Prof. Divangahi’s laboratory.

Rebalancing the immune system

Most flu-related deaths aren't caused by the virus itself, but by an overreaction of the immune system, said the researchers. This suggests the true danger lies in the host’s own immune response. However, how the immune system becomes so imbalanced remains poorly understood.

“Beta-glucan is found in the cell walls of all fungi, including some that live in and on our bodies as part of the human microbiome,” explained Divangahi. “It is tempting to hypothesize that the levels and composition of fungi in an individual could influence how their immune system responds to infections, in part because of beta-glucan.”

With flu season underway and the looming threat of bird flu (H5N1), developing effective therapeutic strategies for respiratory diseases is more critical than ever, he added.

The research was funded by the Canadian Institutes of Health Research.

About the study

“β-Glucan reprograms neutrophils to promote disease tolerance against influenza A virus” by Nargis Khan, Kim Tran and Maziar Divangahi et al., was published in Nature Immunology.

DOI: -https://doi.org/10.1038/s41590-024-02041-2


https://rimuhc.ca/-/new-discovery-could-help-protect-against-influenza?redirect=/fr/
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