Washington University in St. Louis

Immune cell implicated in development of lung disease following viral infection

Findings could help explain how asthma, COPD, severe COVID-19 are triggered

Newswise — Scientists at Washington University School of Medicine in St. Louis have implicated a type of immune cell in the development of chronic lung disease that sometimes is triggered following a respiratory viral infection. The evidence suggests that activation of this immune cell — a type of guardian cell called a dendritic cell — serves as an early switch that, when activated, sets in motion a chain of events that drives progressive lung diseases, including asthma and chronic obstructive pulmonary disease (COPD).

The new study, published in The Journal of Immunology, opens the door to potential preventive or therapeutic strategies for chronic lung disease. More immediately, measuring the levels of these dendritic cells in clinical samples from patients hospitalized with a viral infection, such as influenza or COVID-19, could help doctors identify which patients are at high risk of respiratory failure and death.

Studying mice with a respiratory viral infection that makes the animals prone to developing chronic lung disease, the researchers showed that these dendritic cells communicate with the lining of the airway in ways that cause the airway-lining cells to ramp up their growth and inflammatory signals. The inflammation causes airway-lining cells to grow beyond their normal boundaries and turn into cells that overproduce mucus and cause inflammation, which in turn causes cough and difficulty breathing.

“We’re trying to understand how a viral infection that seems to be cleared by the body can nevertheless trigger chronic, progressive lung disease,” said senior author Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine. “Not everyone experiences this progression. We believe there’s some switch that gets flipped, triggering the bad response. We’re identifying that switch and ways to control it. This work tells us that this type of dendritic cell is sitting right at that switch point.”

Holtzman’s past work had implicated the lining of the airway — where the viral infection takes hold — as the likely trigger for this process.

“But this study suggests that the cascade starts even further upstream,” said Holtzman, also director of the Division of Pulmonary and Critical Care Medicine. “Dendritic cells are telling the cells lining the airway what to do. There’s more work to be done, but this data tells us that the dendritic cells play an important role in getting the airway-lining cells onto the wrong path.”

Holtzman calls this dendritic cell a type of sentinel because its job is to detect an invading virus and trigger the body’s initial immune response against the infection. The problem comes when the cell doesn’t shut down properly after the threat has passed.

“Many people never develop chronic lung disease after a viral infection,” Holtzman said. “But others have a genetic susceptibility to this type of disease. People who are susceptible to virus-triggered disease include patients with asthma, COPD, and viral infections such as COVID-19. It’s really critical to look for ways to fix this disease response and prevent the problems that might occur after the virus has gone.”

In the meantime, Holtzman said, high levels of these dendritic cells and their products in the lungs of hospitalized patients could serve as a warning to doctors that such patients are likely to develop severe disease and should be provided with respiratory interventions and other supportive therapies that are precisely tailored to their disease process.

“Similarly, if this process is not underway, the patient might be more likely to avoid these types of long-term problems,” Holtzman said. “We’re pursuing this line of research to help improve prediction of severe lung disease after infection and to provide companion therapies that could prevent this switch from being flipped or flip it back to reverse the disease.”

###

This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID), grant number R01 AI130591 and the National Heart, Lung, and Blood Institute (NHLBI), grant number R35 HL145242, both of the National Institutes of Health (NIH); the Cystic Fibrosis Foundation; and the Hardy Trust and Schaeffer Funds.

Wang X, Wu K, Keeler SP, Mao D, Agapov EV, Zhang Y, Holtzman MJ. TLR3-activated monocyte-derived dendritic cells trigger progression from acute viral infection to chronic disease in the lung. The Journal of Immunology. Jan. 29, 2021.

Washington University School of Medicine’s 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

SEE ORIGINAL STUDY



Filters close

Showing results

110 of 5857
Released: 22-Jun-2021 5:10 PM EDT
Tecnología de inteligencia artificial y ECG puede rápidamente descartar infección por COVID-19
Mayo Clinic

La inteligencia artificial puede ofrecer un manera de determinar con exactitud que una persona no está infectada con la COVID-19. Un estudio internacional y retrospectivo descubrió que la infección por SARS-CoV-2, el virus que causa la COVID-19, provoca sutiles cambios eléctricos en el corazón. Un electrocardiograma (ECG) mediado por inteligencia artificial detecta estos cambios y puede servir como una prueba rápida y confiable para descartar la infección por COVID-19.

Released: 22-Jun-2021 4:45 PM EDT
Penn Medicine to Use $1M from City of Philadelphia for Additional Community Vaccination Clinics
Perelman School of Medicine at the University of Pennsylvania

Penn Medicine will continue its collaboration with the West and Southwest Philadelphia communities to operate a series of COVID-19 vaccine clinics in partnership with community organizations, faith-based institutions, restaurants, barbershops, and even professional sports teams thanks to $1 million in funding from the City of Philadelphia, in partnership with PMHCC.

Released: 22-Jun-2021 12:30 PM EDT
Political Variables Carried More Weight Than Healthcare in Government Response to COVID-19
Binghamton University, State University of New York

Political institutions such as the timing of elections and presidentialism had a larger influence on COVID-19 strategies than the institutions organizing national healthcare, according to a research team led by a professor at Binghamton University, State University of New York.

22-Jun-2021 12:00 PM EDT
Study Testing How Well COVID-19 Vaccine Prevents Infection and Spread of SARS-CoV-2 Among University Students Now Expands to Include Young Adults Beyond the University Setting
Covid-19 Prevention Network (CoVPN)

The Prevent COVID U study, which launched in late March 2021 to evaluate SARS-CoV-2 infection and transmission among university students vaccinated with the Moderna COVID-19 Vaccine, has expanded beyond the university setting to enroll young adults ages 18 through 29 years and will now also include people in this age group who choose not to receive a vaccine.

Newswise: First Wave COVID-19 Data Underestimated Pandemic Infections
18-Jun-2021 8:30 AM EDT
First Wave COVID-19 Data Underestimated Pandemic Infections
American Institute of Physics (AIP)

Two COVID-19 pandemic curves emerged within many cities during the one-year period from March 2020 to March 2021. Oddly, the number of total daily infections reported during the first wave is much lower than that of the second, but the total number of daily deaths reported during the first wave is much higher than the second wave.

Newswise: PNNL AI Expert Harnesses Open-Source Data to Understand Human Behavior
Released: 22-Jun-2021 9:55 AM EDT
PNNL AI Expert Harnesses Open-Source Data to Understand Human Behavior
Pacific Northwest National Laboratory

PNNL researchers used natural language processing and deep learning techniques to reveal how and why different types of misinformation and disinformation spread across social platforms. Applied to COVID-19, the team found that misinformation intended to influence politics and incite fear spreads fastest.

Released: 22-Jun-2021 8:30 AM EDT
Engineering Nanobodies As Lifesavers When SARS-CoV-2 Variants Attack
Ohio State University

Scientists are pursuing a new strategy in the protracted fight against the SARS-CoV-2 virus by engineering nanobodies that can neutralize virus variants in two different ways.

Released: 21-Jun-2021 3:45 PM EDT
Rare Neurological Disorder Documented Following COVID-19 Vaccination
American Neurological Association (ANA)

In two separate articles in the Annals of Neurology, clinicians in India and England report cases of a rare neurological disorder called Guillain-Barré syndrome after individuals were vaccinated against COVID-19.

Newswise: New Analysis reveals link between birthdays and COVID-19 spread during the height of the pandemic
17-Jun-2021 12:10 PM EDT
New Analysis reveals link between birthdays and COVID-19 spread during the height of the pandemic
Harvard Medical School

Risk of SARS-CoV-2 infection increased 30 percent for households with a recent birthday in counties with high rates of COVID-19 Findings suggest informal social gatherings such as birthday parties played role in infection spread at the height of the coronavirus pandemic No birthday-bash infection jumps seen in areas with low rates of COVID-19 Households with children’s birthdays had greater risk of SARS-CoV-2 infection than with adult birthdays

Newswise: COVID-19 dual-antibody therapies effective against variants in animal study
Released: 21-Jun-2021 10:05 AM EDT
COVID-19 dual-antibody therapies effective against variants in animal study
Washington University in St. Louis

A study from Washington University School of Medicine in St. Louis suggests that many, but not all, COVID-19 therapies made from combinations of two antibodies are effective against a wide range of virus variants, and that combination therapies appear to prevent the emergence of drug resistance.


Showing results

110 of 5857

close
0.98227