Dr. Maziar Divangahi and his research team have uncovered a surprising downside to trained immunity, a process that enhances the immune system’s memory and reactivity. While previous studies suggested that beta-glucan, a molecule from fungi, can reduce lung damage during viral infections like influenza by affecting neutrophils, new findings published in eLife reveal that beta-glucan may actually worsen lung damage under certain inflammatory conditions by reprogramming alveolar macrophages. These macrophages, which reside in the lungs and clear harmful particles, became hyper-responsive after exposure to beta-glucan, leading to greater lung injury when the mice were later exposed to infection-like stimuli.
The study demonstrated that this damaging immune response required signals from infections and interactions with other immune cells, and did not follow traditional immune pathways. When these reprogrammed macrophages were transferred into other mice, they reproduced the inflammation, confirming their role in the damage. This discovery sheds light on the complex and context-dependent nature of immune memory in the lungs. It may help explain why some individuals are more vulnerable to severe inflammation, such as during sepsis, and cautions that boosting trained immunity, such as through supplements, might have unintended harmful effects in the lungs.
While trained immunity is being explored to enhance vaccine responses and disease resistance, this study highlights the importance of understanding its potential risks, especially in delicate tissues like the lungs. The findings underscore the need for careful evaluation of immune-boosting strategies that involve trained immunity, particularly in individuals prone to inflammatory lung conditions.
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β-Glucan reprograms alveolar macrophages via neutrophil/IFNγ axis in a murine model of lung injury. Prevel R, Pernet E, Tran KA, Sadek A, Sadeghi M, Lapshina E, Jurado LF, Kristof AS, Moumni M, Poschmann J, Divangahi M. Elife. 2025 Jul 8;13:RP102068.
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Study reveals trained immunity may cause lung damage. Discovery could help explain why some people are more vulnerable to lung damage during severe inflammation. The Institute News. July 17, 2025.