β-Glucan reprograms alveolar macrophages via neutrophil/IFNγ axis in a murine model of lung injury

Alveolar macrophages (AMs) reside in the lower airways and play a crucial role in lung health and response to sterile inflammation and infections. AMs possess remarkable adaptability to different environmental challenges that can persist through their memory capacity (trained immunity). β-Glucan has...

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Main Authors: Renaud Prevel, Erwan Pernet, Kim A Tran, Abderrahmane Sadek, Mina Sadeghi, Elizabeth Lapshina, Leonardo F Jurado, Arnold S Kristof, Mohieddine Moumni, Jeremie Poschmann, Maziar Divangahi
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-07-01
Series:eLife
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Online Access:https://elifesciences.org/articles/102068
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Summary:Alveolar macrophages (AMs) reside in the lower airways and play a crucial role in lung health and response to sterile inflammation and infections. AMs possess remarkable adaptability to different environmental challenges that can persist through their memory capacity (trained immunity). β-Glucan has been characterized as a potent inducer of central trained immunity by reprogramming haematopoietic stem cells in the bone marrow. In the present study, we show that systemic administration of β-glucan in mice induces peripheral trained immunity by reprogramming AMs in the lungs, in a Dectin1-independent manner. We furthermore demonstrate that AM reprogramming at both the transcriptional and metabolic levels exacerbate lung injury following bacterial (lipopolysaccharide) or viral (polyI:C) challenges via a neutrophil/IFN-γ-dependent manner. These findings identify an additional facet of β-glucan in trained immunity involving AM reprogramming and shed light on the potential detrimental effects of trained immunity.
ISSN:2050-084X