
In the diabetic mice they identified a dysfunction of certain lung dendritic cells, the immune cells that orchestrate a targeted immune response against pathogenic infection. “High blood sugar levels severely disrupt certain subsets of dendritic cells in the lung, preventing these gatekeepers from sending the molecular messages that activate the critically important immune response,” said Samuel Nobs, a postdoctoral researcher at the Institute. “As a result, the infection rages on, uncontrolled.” Importantly, the scientists discovered how high sugar levels in diabetic mice disrupt the normal function of lung dendritic cells during infection. Altered sugar metabolism in these cells led to the accumulation of metabolic byproducts that markedly disrupted the normal regulation of gene expression, leading to aberrant immune protein production. “This could explain why the functioning of these cells is disturbed in diabetes, and why the immune system is unable to generate an effective anti-infection defence,” said Aleksandra Kolodziejczyk, another postdoctoral student at the Institute. The scientists next found that tight control of blood sugar levels by insulin supplementation prompted the dendritic cells to regain their capacity to generate a protective immune response that could prevent the cascade of events leading to a severe, life-threatening viral lung infection. Alternatively, administration of small molecules reversing the sugar-induced regulatory impairment corrected the dendritic cells’ dysfunction and enabled them to generate a protective immune response despite the presence of high sugar levels.