Cigarette smoke changes the function of immune cells in the lungs

Cigarette smoking is widespread and deadly, but our understanding of how cigarette smoke actually causes severe respiratory disease is incomplete, which makes it difficult to find effective treatments. This greatly hinders development. Australian researchers today revealed how several chemicals in tobacco smoke and e-cigarettes change the function of an important type of immune cell in the lungs.

The study was published in the journal Jan. 17. medicine journal (gem), these changes may make cigarette smokers and people exposed to second-hand and third-hand smoke more susceptible to respiratory infections and worsen smoking-related inflammatory diseases such as chronic obstructive pulmonary disease. It suggests (COPD).

Smoking is known to impair the immune system's response to infections and make them worse. inflammation In the lungs, it can cause or worsen COPD, the third leading cause of death worldwide. People with COPD are more susceptible to influenza infections, which can worsen the inflammation of the airways and accelerate the destruction of air sacs in the lungs, worsening the underlying disease. Currently, there are no effective treatments for COPD.

According to Dr. Wael Awad of Monash University's Biomedical Discovery Institute and lead author of the new study. gem The study concludes, “To date, it is unclear the mechanisms underlying the biased immune response in people exposed to cigarette smoke and how it relates to smoking-related diseases such as COPD. It remains the same.”

Professor Jamie Rossjohn from Monash University's Biomedical Discovery Institute, Professor David P. Fairley from the Institute of Molecular Biosciences at the University of Queensland, and Professor Alexandra J. Corbett from the University of Melbourne, based at the Peter Doherty Institute for Infectious Diseases. led the research in collaboration with and Immunology, and Professor Philip M. Hansbro of the Centenary Institute and the University of Technology Sydney.

In this study, researchers examined the effects of cigarette smoke on mucosa-associated invariant T (MAIT) cells, a type of immune cell found in the lungs and other tissues of the body. MAIT cells help fight off bacterial and viral infections and promote inflammation and tissue repair.

MAIT cells are activated by a protein called MR1, which is present in nearly every cell in the body. MR1 recognizes chemicals produced by bacteria and presents them on the surface of infected cells to activate MAIT cells and mount an immune response. “We know that smoke from cigarettes, wildfires, cooking, car exhaust and combustion waste poses serious health risks, but we don't know how specific components of smoke affect the immune system. And we still know surprisingly little about how they affect multiple parts of the human body,'' Professor Fairley said.

We hypothesized that some of the more than 20,000 chemicals found in cigarette smoke that smokers inhale may also bind to MR1 and influence the activity of MAIT cells in the lungs. ”

Dr. Wael Awad, Monash University Biomedical Discovery Institute

The researchers used computer modeling to predict which components of cigarette smoke are recognized by MR1, and found that not only do some of these molecules bind to proteins, but also their abundance on the cell surface. was found to increase or decrease. These chemicals, including a benzaldehyde derivative also used as a flavoring agent in cigarettes and e-cigarettes, blocked the activation of human MAIT cells by compounds produced by bacteria.

The research team then studied the effects of cigarette smoke on MAIT cells in human blood and mice and showed that MAIT cells become less functional. Mice repeatedly exposed to cigarette smoke developed symptoms of lung disease, which worsened when they were also infected with influenza. Researchers found that long-term exposure to cigarette smoke alters the defenses provided by MAIT cells in mice, reducing their ability to fight off influenza infection and making them more susceptible to developing COPD disease.

“We found that mice deficient in MAIT cells were also protected against COPD caused by cigarette smoke, had reduced levels of lung inflammation, and showed no tissue deterioration in the air sacs of the lungs,” Professor Hansbro said. Ta.

“This research shows the power of collaboration and the insights that can be gained from interdisciplinary science,” Professor Corbett said.

“Overall, our study revealed that components of cigarette smoke bind to the protein MR1 and can reduce the function of protective immune cells called MAIT cells, which can reduce the risk of infection. This increases susceptibility to lung disease and worsens the progression of lung disease,” Dr. Awad said. Researchers now plan to investigate exactly which MAIT cellular pathways are affected by cigarette smoke to learn how to better treat COPD and other lung diseases.