Q&A: IL-13 protects patients with allergic asthma against effects of SARS-CoV-2 infection
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The Th2 cytokine IL-13 appeared to play a significant role in protecting people with allergic asthma against the damaging effects of SARS-CoV-2 infection, according to a study published in Proceedings of the National Academy of Sciences.
After infecting human airway epithelial cell cultures with the virus, the researchers found that the protein angiotensin-converting enzyme 2 (ACE2) governed which cell types were infected and the viral load found in this cell population.
Further examination revealed the virus left ciliated cells and severe cytopathogenesis, culminating in ciliated cells packed with virions shedding away from the airway surface. This shedding created a viral reservoir that spread the virus and increased the potential for infected cells to relocate to deeper lung tissue, the researchers wrote.
The MUC5AC mucus protein, which the body secretes to trap invading viruses, also appeared depleted inside cells as the virus load kept increasing. However, IL-13 increases MUC5AC secretion in the lungs when patients with asthma face an allergen.
The researchers then treated human airway cells with IL-13 and found significant reductions in viral titers, viral mRNA, infected cell shedding rates and overall numbers of infected cells, even when mucus was removed from the cultures.
Further, the researchers found that IL-13 upregulated genes that control glycoprotein synthesis, ion transport and antiviral processes while reducing ACE2, which is a viral receptor, as well as the amount of virus inside cells and cell-to-cell viral transmission.
Noting that IL-13 significantly affects viral entry into cells, replication inside cells and virus spread, Healio spoke with Camille Ehre, PhD, assistant professor of pediatrics at the University of North Carolina School of Medicine, to find out more about how this cytokine protects patients with allergic asthma and others from SARS-CoV-2.
Healio: Generally, how well do patients with allergic asthma fare during SARS-CoV-2 infection compared with patients who do not have allergic asthma?
Ehre: So far, only allergic asthmatics have been found to be less susceptible to COVID-19 severity. However, patients with permanent lung damage may experience further complications due to SARS-CoV-2 infection.
Healio: Why did you select IL-13 as a focus for your study?
Ehre: Initially, we wanted to see if MUC5AC or mucus overproduction altered SARS-CoV-2 infectivity. We knew from our previous studies that MUC5AC showed protective effects against other viruses, such as influenza, and we also knew that IL-13 upregulated MUC5AC. Thus, we tested the effects of IL-13 pretreatment on SARS-CoV-2 infectivity.
We demonstrated that MUC5AC hyperproduction had some effects but, to our surprise, there were additional protective effects that appeared to be unrelated to mucus hyperproduction. We investigated different molecular pathways that could be involved in these protective mechanisms, one of them being the downregulation of the ACE2 protein, the SARS-CoV-2 receptor.
Healio: What are the primary effects that IL-13 has on the immune system to fight SARS-CoV-2 infection?
Ehre: As shown in the bulk RNA sequencing data, there are several gene sets that are altered by IL-13, and a number of them could have an impact on SARS-CoV-2 infections. Importantly, the typical interferon stimulated genes shown to be upregulated in response to SARS-CoV-2 infection were not induced by IL-13. The most relevant gene sets that were upregulated by IL-13 were protease inhibitor genes, shown to have antiviral activities, and glycoprotein synthesis genes, shown to have shielding properties against pathogens.
Healio: Were there any particularly surprising or significant findings in this study?
Ehre: Yes. As explained above, we expected mucus hypersecretion to have protective effects. But we were surprised to maintain some level of protection even after the removal of mucus, suggesting that other molecular alterations induced by the Th2 cytokine played a role.
Healio: Is there potential for treatment that can replicate these effects among patients who do not have allergic asthma?
Ehre: We cannot treat patients with pro-inflammatory cytokines. However, discovering the precise mechanism that elicits protection would be key for therapeutic approaches, but more work is needed to further investigate these pathways.
Healio: What is the next stage in this research?
Ehre: We are going to treat mice with different genetic backgrounds to try to understand the effects of Th2 cytokines in the whole lung. It will be important to study how inflammatory cells and the virus are interacting in these animals.
Reference:
- Why are people with allergic asthma less susceptible to severe COVID? https://news.unchealthcare.org/2022/03/why-are-people-with-allergic-asthma-less-susceptible-to-severe-covid/. Posted March 30, 2022. Accessed April 1, 2022.