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January 2025 | Melbourne, Australia — In a groundbreaking study, Australian researchers have discovered how cigarette smoke, including e-cigarette vapors, alters the function of immune cells in the lungs, making smokers and those exposed to second- and third-hand smoke more vulnerable to respiratory infections and severe lung diseases. This research sheds light on the molecular mechanisms behind chronic respiratory illnesses like chronic obstructive pulmonary disease (COPD), a leading cause of death worldwide.
The study, recently published in the Journal of Experimental Medicine, reveals that harmful chemicals in cigarette smoke impair the activity of a vital immune cell called Mucosal-Associated Invariant T (MAIT) cells. These immune cells, crucial for defending against infections, play a key role in maintaining lung health. According to Dr. Wael Awad from Monash University’s Biomedicine Discovery Institute, this breakthrough offers new insights into the long-standing question of how cigarette smoke contributes to immune dysfunction and disease progression in the lungs.
“Until now, the exact mechanisms behind the immune dysfunction in people exposed to cigarette smoke and its association with diseases like COPD were unclear,” Dr. Awad stated. “Our study identifies how certain chemicals in cigarette smoke alter MAIT cell function, which can worsen infections and increase inflammation in the lungs.”
Cigarette smoke is known to damage the immune system, making it more difficult for the body to respond to infections. In particular, it accelerates lung inflammation, a characteristic of COPD, which can be exacerbated by influenza infections. COPD, characterized by difficulty breathing, lung damage, and frequent respiratory infections, currently has no effective treatment and is the third leading cause of death globally.
Researchers found that certain chemicals in cigarette smoke, particularly benzaldehyde derivatives (also used in e-cigarettes), bind to a protein called MR1, which is responsible for activating MAIT cells. This disruption hampers the immune system’s ability to fight infections, making smokers more susceptible to diseases like influenza, which worsens COPD. The findings also suggest that prolonged exposure to these chemicals impairs the body’s defense mechanisms, contributing to lung tissue damage and disease progression.
The team’s study used computer modeling to predict how cigarette smoke components interact with MR1. Their research demonstrated that these chemicals block the activation of MAIT cells by bacteria-derived compounds, further compromising immune responses. Laboratory tests on human blood and mice confirmed that cigarette smoke reduced MAIT cell activity, leading to symptoms of lung disease that were aggravated by influenza infection.
In experiments involving mice exposed to long-term cigarette smoke, the researchers observed that those lacking MAIT cells exhibited reduced inflammation and tissue damage in the lungs, providing evidence that MAIT cells are central to smoke-induced lung disease. These findings open new possibilities for developing therapies aimed at restoring the protective functions of these immune cells.
Professor Jamie Rossjohn, co-leader of the study, emphasized the importance of collaborative research in tackling complex health issues. “This study highlights how interdisciplinary science can unravel the intricate ways cigarette smoke impacts immune function and lung health,” he said.
The next steps in the research will focus on identifying the specific MAIT cell pathways altered by cigarette smoke, with the goal of improving treatments for COPD and other lung-related diseases.
The study offers hope that a better understanding of how cigarette smoke damages the immune system may lead to more effective therapies for those suffering from COPD and other respiratory conditions.
For more information:
Wael Awad et al., Cigarette Smoke Components Modulate the MR1-MAIT Axis, Journal of Experimental Medicine (2024). DOI: 10.1084/jem.20240896
