IL-13 Stimulating Mucus Secretion
Inhibits Entire COVID-19 Infection Process
[Asia Economy Reporter Na Ye-eun] A study has found that patients with allergic asthma are particularly resistant to Omicron infection. However, patients with similar chronic diseases such as chronic obstructive pulmonary disease (COPD) or emphysema have been shown to be at very high risk of severe COVID-19.
The study, led by Assistant Professor Camille Ehre of the Marsico Lung Institute at the University of North Carolina (UNC), was published on the 30th of last month (local time) in the Proceedings of the National Academy of Sciences (PNAS).
The research team stated that "the inflammatory cytokine (immune protein) 'interleukin-13' (IL-13) present in allergic asthma patients played a key role in blocking Omicron." They explained that IL-13 controls the expression of ACE2 (angiotensin-converting enzyme) in host cells, thereby inhibiting coronavirus cell infection.
The team investigated the foreign substance clearance mechanism of airway epithelial cells. By analyzing the gene sequences of airway epithelial cells infected with COVID-19, they found a distinctive feature in the ACE2 receptor. Depending on the level of ACE2 expression, the type of infected cells and the viral load after infection varied.
The researchers also observed, through electron microscopy, the collective escape of the virus from ciliated cells of the mucus-covered airway epithelium. They confirmed that severe pathological changes occurred within cells due to viral infection.
The team reported, "When these changes accumulate to a peak, ciliated cells filled with virus particles trapped in mucus can detach entirely from the airway surface."
Professor Ehre explained, "The detached ciliated cells can act as a kind of viral reservoir, aiding in the spread and transmission. Additionally, the possibility of infected cells spreading deep into lung tissue increases."
The major mucus protein (MUC5AC) used to trap invading viruses was found to be significantly deficient. However, the viral load continued to increase because the viral infection progressed so aggressively that it overwhelmed the mucus-secreting cells.
The research team focused on the fact that this mucus protein is excessively secreted in allergic asthma patients. It was also known that when asthma patients are exposed to allergic antigens, IL-13 stimulates mucus protein secretion in the lungs.
The team applied IL-13 to human airway epithelial cells to create a model similar to the airways of asthma patients.
They then measured viral titer, mRNA levels, the rate of ciliated cell detachment, and the total number of infected cells. Surprisingly, all these values were significantly reduced. Even when mucus was completely removed from the airway epithelial cells, the reduced values did not change.
The researchers said, "This suggests that factors other than mucus contribute to the antiviral effect of IL-13," adding, "This question was resolved through large-scale RNA sequencing analysis."
They continued, "IL-13 uniformly upregulated control genes important for airway immune defense, such as glycoprotein synthesis, ion transport, and antiviral processes. IL-13 also lowered ACE2 expression and was involved in suppressing intracellular viral load and intercellular transmission," they added.
IL-13 had a significant impact on all stages of the virus lifecycle?from cell entry, post-entry replication, to post-replication spread?and this action of IL-13 ultimately prevented COVID-19 from causing severe lung infections and other complications.
Professor Ehre emphasized, "We reaffirmed that to prevent COVID-19 patients from progressing to severe disease, treatment should be administered as early as possible."
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