β-glucan reprograms alveolar macrophages via neutrophil/IFNγ axis to promote lung injury

Prevel, R.; Pernet, E.; Tran, K. A.; Sadek, A.; Sadeghi, M.; Lapshina, E.; Jurado, L.; Kristof, A. S.; Moumni, M.; Poschmann, J.; Divangahi, M.

doi:10.1101/2024.09.02.610842

bioRxiv · 10.1101/2024.09.02.610842

β-glucan reprograms alveolar macrophages via neutrophil/IFNγ axis to promote lung injury

Prevel, R.·Pernet, E.·Tran, K. A.·Sadek, A.·Sadeghi, M.·Lapshina, E.·Jurado, L.·Kristof, A. S.·Moumni, M.·Poschmann, J.·Divangahi, M.

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Abstract

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). {beta}-glucan has been characterized as a potent inducer of central trained immunity by reprogramming hematopoietic stem cells (HSCs) in the bone marrow. In the present study, we show that systemic administration of {beta}-glucan induces peripheral trained immunity by reprogramming alveolar macrophages (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 (LPS) or viral (polyI:C) challenges via a neutrophil/IFN-{gamma} dependent manner. These findings identify an additional facet of {beta}-glucan in trained immunity involving AM reprogramming and shed light on the potential detrimental effects of trained immunity.

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Prevel, R., Pernet, E., Tran, K. A., Sadek, A., Sadeghi, M., Lapshina, E., Jurado, L., Kristof, A. S., Moumni, M., Poschmann, J., Divangahi, M.. 2024-09-03. β-glucan reprograms alveolar macrophages via neutrophil/IFNγ axis to promote lung injury. https://doi.org/10.1101/2024.09.02.610842

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