Fungal Molecule Can Trigger Harmful Overreactions in Lung Immune Cells

Recent research has uncovered how a common fungal component can profoundly alter immune cells in the lungs, leading to exaggerated responses to infection signals and heightened lung damage. The study reveals that exposure to β-glucan, a molecule found in fungi, reprograms alveolar macrophages—the immune cells that reside permanently within the lung's air sacs—to become hyper-reactive. When these reprogrammed cells encounter bacterial or viral mimics, they produce increased inflammatory molecules and recruit additional immune cells like neutrophils, driving more severe inflammation and tissue injury.

The scientists administered a single dose of purified β-glucan to mice and observed their response to infection-mimicking agents. They found that these mice experienced more intense lung injury, characterized by poorer airflow, thicker alveolar walls, and increased immune cell infiltration. Notably, this effect was independent of the traditional receptor Dectin-1 and did not require type I interferons, but instead depended on interferon-gamma and neutrophils.

Further analyses demonstrated that trained alveolar macrophages exhibited altered gene expression and energy metabolism consistent with long-lasting immune memory. The reprogramming persisted even after macrophages were depleted and reintroduced, indicating a lasting change within the cells.

This discovery suggests that systemic signals like β-glucan can induce immune memory in lung macrophages, which could have both protective and harmful consequences. While trained immunity may boost defenses against infections, in certain contexts, such as sepsis, it may provoke excessive inflammation and tissue damage.

The findings have significant implications for understanding lung inflammation and developing strategies to mitigate immune overreactions caused by fungal exposures. Ultimately, this research expands our knowledge of how immune memory in the lungs can be both beneficial and detrimental, depending on the situation.

Source: https://medicalxpress.com/news/2025-07-common-fungal-molecule-prime-lung.html