Cigarette smoke is known to impair the immune system’s response to infections and promote lung inflammation, but the mechanisms behind these effects have remained unclear.
RT’s Three Key Takeaways:
- Cigarette Smoke Impairs Lung Immunity: Chemicals in cigarette smoke and e-cigarettes disrupt the function of mucosal-associated invariant T (MAIT) cells, a key immune cell in the lungs, making individuals more vulnerable to infections and inflammatory diseases like COPD.
- Immune Disruption Linked to MR1 Protein: Researchers found that cigarette smoke chemicals bind to the MR1 protein, altering its ability to activate MAIT cells, which compromises the immune system’s defense against bacterial and viral infections.
- New Insights Into COPD Progression: Long-term exposure to cigarette smoke reduces MAIT cell function, worsening lung disease and increasing susceptibility to respiratory infections, highlighting potential therapeutic targets for treating COPD.
Cigarette smoking is widespread and deadly, yet our understanding of how cigarette smoke actually causes serious respiratory illnesses is incomplete, which has severely hampered the development of effective treatments.
Australian researchers have revealed how multiple chemicals found in cigarette smoke and e-cigarettes alter the function of a key type of immune cell found in the lungs.
The study, published in the Journal of Experimental Medicine, suggests that these alterations make cigarette smokers, and those exposed to second- and third-hand smoke, more susceptible to respiratory infections and worsen smoking-related inflammatory diseases such as chronic obstructive pulmonary disease (COPD).
Cigarette smoking is known to impair the immune system’s response to infections and promote inflammation in the lungs that can lead to or exacerbate COPD. COPD patients are more susceptible to influenza infections that can, in turn, worsen the underlying disease by increasing airway inflammation and promoting the destruction of the lung’s air sacs. There are currently no effective treatments for COPD.
Immune Cells Impaired by Cigarette Smoke
“Until now, the mechanisms underlying the skewed immune responses in people exposed to cigarette smoke and how they are related to smoke-associated diseases like COPD remain unclear,” says Wael Awad, PhD, from Monash University’s Biomedicine Discovery Institute and first author on the new study, in a release.
In the study, the researchers looked at the effects of cigarette smoke on mucosal-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 can promote inflammation or tissue repair.
MAIT cells are activated by a protein called MR1 that is found in almost every cell of the body. MR1 recognizes chemicals produced by bacteria and presents them at the surface of infected cells in order to activate MAIT cells and initiate an immune response.
“While we know that smoke from cigarettes, bushfires, cooking, vehicle exhausts, and burning waste pose significant health risks, we still surprisingly know relatively little about how the specific components of smoke affect our immune system and how they impact multiple parts of the human body,” says co-author of the study David P. Fairlie of the Institute for Molecular Bioscience at University of Queensland in a release.
Components of Smoke Disrupt Immune Function
Awad adds, “We suspected that some of the more than 20,000 chemicals present in cigarette smoke that smokers inhale might also bind to MR1 and influence the activity of MAIT cells in the lungs.”
The researchers used computer modeling to predict which components of cigarette smoke might be recognized by MR1 and found that several of these molecules not only bound to the protein but also either increased or decreased its amounts on the surface of cells. These chemicals, including benzaldehyde derivatives that are also used as flavorings in cigarettes, e-cigarettes, blocked activation of human MAIT cells by compounds produced by bacteria.
The research team then studied the effects of cigarette smoke on MAIT cells from human blood and mice and showed they reduced MAIT cell function. Mice repeatedly exposed to cigarette smoke developed symptoms of lung disease and this was worsened if also infected by influenza. Researchers found that long-term exposure to cigarette smoke altered the protection provided to mice by their MAIT cells, making them less able to fight off influenza infections and more prone to the development of COPD disease.
Implications for COPD and Future Research
“We found that mice lacking MAIT cells were also protected from cigarette smoke–induced COPD, showing reduced levels of lung inflammation and no tissue deterioration in their lung’s air sacs,” says Philip M. Hansbro, PhD, of the Centenary Institute and University of Technology Sydney and co-author of the study, in a release.
Awad adds in a release, “Overall, our study reveals that components of cigarette smoke can bind to the protein MR1 and reduce the functions of protective immune cells called MAIT cells. This increases susceptibility to infections worsens progression of lung disease.”
The researchers now plan to investigate exactly which MAIT cell pathways are impacted by cigarette smoke in order to learn how to better treat COPD and other lung diseases.