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A groundbreaking study conducted at the Weizmann Institute of Science in Israel has shed light on a critical connection between high blood sugar levels in individuals with diabetes and the increased risk of severe lung infections caused by viruses, bacteria, and fungi.
Researchers conducted experiments on multiple mouse models of both type 1 and type 2 diabetes, exposing them to various viral lung infections. The findings, published in Nature, mirrored observations in diabetic humans, where exposure to lung pathogens such as influenza led to severe and often fatal lung infections in diabetic mice.
The study uncovered that the immune response in diabetic mice, which typically clears infections and aids in tissue healing in non-diabetic subjects, was severely compromised. This impairment resulted in uncontrolled infections, significant lung damage, and eventual fatality.
Delving deeper, the team analyzed gene expression at the individual cell level in over 150,000 single lung cells from infected diabetic and non-diabetic mice. They pinpointed dysfunction in specific lung dendritic cells responsible for orchestrating a targeted immune response against infections.
Lead researcher Samuel Nobs highlighted that elevated blood sugar levels disrupted these vital subsets of dendritic cells in the lungs, preventing them from triggering the necessary immune response. This disruption allowed the infection to persist unchecked.
Crucially, the study revealed how high sugar levels altered the metabolism of these cells, leading to the accumulation of metabolic byproducts that disrupted normal gene expression regulation, resulting in faulty immune protein production.
Postdoctoral student Aleksandra Kolodziejczyk emphasized that this discovery explained the disturbance in cell functioning seen in diabetes and the subsequent inability of the immune system to mount an effective defense against infections.
Encouragingly, the researchers found that tightly controlling blood sugar levels through insulin supplementation helped restore the dendritic cells’ ability to generate a protective immune response, preventing severe, life-threatening lung infections. Additionally, administering specific small molecules reversed the sugar-induced impairment, enabling these cells to mount a defense despite high sugar levels.
These findings offer promising avenues for potential treatments or interventions that could mitigate the heightened risk of severe lung infections in individuals with diabetes by targeting the immune cell dysfunction induced by high blood sugar levels.
