July 24, 2024

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High Blood Sugar Weakens Lung Immunity!

High Blood Sugar Weakens Lung Immunity!



High Blood Sugar Weakens Lung Immunity!

For the first time, scientists have discovered that high blood sugar can lead to a decrease in the antigen presentation ability of lung dendritic cells, increasing the risk of lung infections.

Even after successfully warding off the novel coronavirus, our respiratory system hasn’t had much respite as the weather turns colder this year. Influenza viruses and pneumonia-causing pathogens take turns bombarding us, causing outbreaks of seasonal flu and mycoplasma pneumonia in the fall and winter seasons. (Don’t get confused, mycoplasma is a pathogenic microorganism between bacteria and viruses, not a “new variant of the coronavirus.”)

Research indicates that whether it’s the flu or COVID-19, viral respiratory infections have a particular affinity for “sugar.” Here, sugar refers to high blood sugar. Both type 1 and type 2 diabetes exhibit a significant and unexplained susceptibility to respiratory infections, even leading to fatal lung infections.

Recently, a paper published in the prestigious journal “Nature” has, for the first time, revealed the mechanism behind the increased susceptibility of diabetic patients to viral respiratory infections. It turns out that high blood sugar suppresses the combat capabilities of our lung immune sentinels [1].

High Blood Sugar Weakens Lung Immunity!

The immune sentinels in the lungs, dendritic cells, possess the ability to capture, process, and present pathogen antigens. They transport these antigens to the lung-draining lymph nodes, activating T cells to help us resist the flu. The team led by Eran Elinav from the Weizmann Institute of Science in Israel found that blood sugar plays a crucial regulatory role in lung dendritic cells. High blood sugar alters the epigenetics of dendritic cells, causing immune dysfunction, weakening the immune resistance of high blood sugar mice to viral respiratory infections.

According to statistics, the global number of diabetes patients has steadily risen from 108 million in 1980 to over 500 million today, with a projected increase to 785 million by 2045 [2]. The burden of diseases caused by diabetes is increasing, and respiratory infections are posing continuous challenges. It is essential to explore the intricacies between them.

The team of Eran Elinav initially discovered in mouse experiments that type 1 or type 2 diabetic mice, when infected with influenza virus or other pulmonary pathogens, failed to clear the pathogens promptly. They exhibited higher mortality rates, higher viral loads in the lungs, and reduced infiltration of immune cells into the lungs. The adaptive immune responses mediated by T cells and B cells were severely impaired.

Supplementing with insulin to lower blood sugar levels could reverse these effects, enhancing virus clearance, survival rates, improving immune responses, and controlling lung damage in diabetic mice infected with the flu.

So, where does the problem lie?

Subsequently, the Eran Elinav team used techniques such as single-cell RNA sequencing to analyze over 150,000 mouse lung cells, comparing the differences in gene expression between diabetic and non-diabetic mice after infection with the flu virus.

The results showed that after infection with the flu virus, multiple subgroups of lung dendritic cells in diabetic mice exhibited abnormal gene expression, especially the cDC1 subgroup, the most severely damaged immune cells in the lungs of diabetic mice.

In combination with in vitro culture experiments, researchers found that these lung dendritic cells, in the presence of high glucose either within diabetic mice or in a high-glucose culture environment (50mM), showed no change in cell activity. However, the expression of genes related to antigen presentation was downregulated, and the antigen presentation ability was reduced. The ability to induce T cell immune activation was directly inhibited under high-sugar conditions.

When drugs were injected to specifically deplete dendritic cells in their bodies, the antiviral immunity of diabetic mice was not further compromised. On the other hand, if wild-type mice received lung dendritic cells from influenza-infected diabetic mice, their adaptive immune responses in the lungs were weakened under non-infection conditions, and their ability to clear the virus decreased during influenza infection.

These results indicate that lung dendritic cells are a crucial link connecting high blood sugar with susceptibility to the flu.

Blood sugar and metabolism always go hand in hand.

Indeed, further research suggests that high blood sugar can regulate the function of lung dendritic cells by altering metabolic processes.

Specifically, under high blood sugar conditions, the metabolic pathway in lung dendritic cells converting glucose into acetyl-coenzyme A is enhanced. This results in excessive histone acetylation, causing changes in cell chromatin after epigenetic modification, thereby impairing the gene expression related to dendritic cells and immune function.

Histone acetyltransferase inhibitors (hydrogenated ellagic acid, ANA) can partially rescue the excessive acetylation of dendritic cells and their impact on T cell immunity. Diabetic mice treated with histone acetyltransferase inhibitors showed improved virus clearance after infection with the flu virus.

In summary, this study explains for the first time why diabetic patients are more susceptible to respiratory infections, linking it to high blood sugar damaging the function of lung dendritic cells.

Eran Elinav emphasizes [2] that the results of this study highlight the importance of strict blood sugar control for diabetic patients, especially during viral respiratory infections. Lowering high blood sugar through insulin can improve antiviral immune function.

For diabetic patients who cannot effectively control their blood sugar levels, intervention targeting the excessive acetylation of dendritic cells with drugs may help improve immune dysfunction caused by high blood sugar, alleviate, or even prevent severe lung infections. Local administration through inhalation could minimize side effects and maximize effectiveness, and these approaches are worthy of further clinical trials [2].

References:

[1] Nobs, S.P., Kolodziejczyk, A.A., Adler, L. et al. Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes. Nature (2023). https://doi.org/10.1038/s41586-023-06803-0

[2] https://wis-wander.weizmann.ac.il/life-sciences/why-people-diabetes-are-more-prone-respiratory-risk

High Blood Sugar Weakens Lung Immunity!

References:

[1] Nobs, S.P., Kolodziejczyk, A.A., Adler, L. et al. Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes. Nature (2023). https://doi.org/10.1038/s41586-023-06803-0

[2] https://wis-wander.weizmann.ac.il/life-sciences/why-people-diabetes-are-more-prone-respiratory-risk

(source:internet, reference only)


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