Type III interferons: Protective or harmful in COVID-19?

June 11, 2020

Interferons and other cytokines produced by the immune system are important defenses against viral infections, but as we have seen in COVID-19, they can also contribute to damaging, potentially life-threatening lung inflammation. Recent evidence suggests that one type of interferon, known as type III interferon or interferon lambda (λ), can fight viral infection while limiting this inflammatory damage. That has led to clinical trials to test type III interferon as a treatment for COVID-19.

But in the journal Science, researchers at Boston Children's Hospital, with collaborators in Italy, now provide evidence that type III interferons can increase the risk of life-threatening bacterial "superinfections" in the lung. Superinfections can occur in both influenza and COVID-19, and the investigators caution that type III interferons given later in the course of COVID-19 could do more harm than good.

"Our data indicate that SARS-CoV-2 inhibits interferon production in the upper airways, weakening the immune response and helping the virus survive," says senior investigator Ivan Zanoni, PhD, an immunologist at Boston Children's. "But when the virus reaches the lower airways, there is an exuberant immune response, including upregulation of type III interferons that we think is harmful."

The team first tested samples from patients with severe COVID-19 and healthy controls. Interferon III was not much increased in the patients' nasopharyngeal swab samples, but was markedly elevated in their lung fluid.

The researchers then exposed mice to synthetic viral RNA to mimic the effects of SARS-CoV-2 infection in the lower airways. They showed that interferon III levels rose markedly in the animals' lungs as compared with control mice, and that sustained production of interferon III prevented the lungs from maintaining their protective surface barrier. This, in turn, made the animals more susceptible to lethal bacterial infections from Staphylococcus aureus: experiments showed increased amounts of bacteria and higher mortality as compared with control mice.

"There's still a lot to understand, but it looks like location and timing of interferon production are key," says Zanoni. "Early during SARS-CoV-2 infection, when the virus is in the upper airways, it might be important to intervene with recombinant interferons and other antivirals. But later on, when inflammation is highly increased in the lower airways, it will be important to block the signaling cascade initiated by interferons and other inflammatory cytokines, possibly with the anti-inflammatory drugs."
-end-
Achille Broggi, PhD, Sreya Ghosh, PhD, and Benedetta Sposito of Boston Childrens's Hospital were first authors on the paper. The study was supported by the National Institutes of Health (1R01AI121066, 1R01DK115217, and NIAID-DAIT- NIHAI201700100), the Crohn's and Colitis Foundation (RFA 549868), AIRC (IG 2019Id.23512), Fondazione regionale per la Ricerca Biomedica, FRRB (IANG-CRC CP2_12/2018), and Ministero della Salute, Ricerca Finalizzata (RF-2018-12367072).

About Boston Children's Hospital

Boston Children's Hospital is ranked the #1 children's hospital in the nation by U.S. News & World Report and is the primary pediatric teaching affiliate of Harvard Medical School. Home to the world's largest research enterprise based at a pediatric medical center, its discoveries have benefited both children and adults since 1869. Today, 3,000 researchers and scientific staff, including 9 members of the National Academy of Sciences, 21 members of the National Academy of Medicine and 12 Howard Hughes Medical Investigators comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's is now a 415-bed comprehensive center for pediatric and adolescent health care. For more, visit our Discoveries blog and follow us on social media @BostonChildrens, @BCH_Innovation, Facebook and YouTube.

Boston Children's Hospital

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.