For decades, it has been known that people with diabetes are at a substantially increased risk of developing severe lung disease if they become infected with viruses such as influenza, as well as with bacteria and fungi.
When the COVID-19 pandemic started in early 2020, this mysterious phenomenon gained even more pressing importance: It became clear that people with diabetes were at a significantly higher risk of coming down with severe, even fatal, lung disease after developing a serious form of the virus, but no one understood why. In fact, some 35 percent of people with COVID-19 who died during the pandemic had diabetes.
Now, research conducted at the Weizmann Institute of Science and published in Nature has revealed how, in diabetics, high levels of blood sugar disrupt the function of key cell subsets in the lungs that regulate the immune response. It also identifies a potential strategy for reversing this susceptibility and saving lives.
Prof. Eran Elinav’s team in his lab at Weizmann, headed by Drs. Samuel Nobs, Aleksandra Kolodziejczyk and Suhaib K. Abdeen, subjected multiple mouse models of types 1 and 2 diabetes to a variety of viral lung infections.
Just as in diabetic humans, in all these models the diabetic mice developed a severe, fatal lung infection following exposure to lung pathogens such as influenza. The immune reaction, which in nondiabetics eliminates the infection and drives tissue healing, was severely impaired in the diabetic mice, leading to uncontrolled infection, lung damage and eventual death.
Next, to decode the basis of this heightened risk, the team performed an evaluation of gene expression on the level of individual cells, in more than 150,000 single lung cells of infected diabetic and nondiabetic mice.
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.
The scientists next explored ways to prevent the harmful effects of high sugar levels in lung dendritic cells, as a means of lowering the infection’s risk in diabetic animals. Indeed, 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.
With over 500 million people around the world affected by diabetes, and with diabetes incidence expected to rise over the next decades, the new research has significant, promising clinical implications.
Samuel Philip Nobs, Aleksandra A. Kolodziejczyk, Lital Adler, Nir Horesh, Christine Botscharnikow, Ella Herzog, Gayatree Mohapatra, Sophia Hejndorf, Ryan-James Hodgetts, Igor Spivak, Lena Schorr, Leviel Fluhr, Denise Kviatcovsky, Anish Zacharia, Suzanne Njuki, Dinorah Barasch, Noa Stettner, Mally Dori-Bachash, Alon Harmelin, Alexander Brandis, Tevie Mehlman, Ayelet Erez, Yiming He, Sara Ferrini, Jens Puschhof, Hagit Shapiro, Manfred Kopf, Arieh Moussaieff, Suhaib K. Abdeen, Eran Elinav. Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes. Nature, 2023; 624 (7992): 645 DOI: 10.1038/s41586-023-06803-0
Weizmann Institute of Science. (2023, December 21). Why people with diabetes are more prone to respiratory risk. ScienceDaily. Retrieved December 28, 2023 from www.sciencedaily.com/releases/2023/12/231221012854.htm