Cigarette smoking is a prevalent and lethal habit, yet our understanding of its role in causing severe respiratory diseases remains incomplete, hindering the development of effective treatments. A recent breakthrough by Australian scientists has shed light on how various chemicals in cigarette smoke and e-cigarettes impair the function of crucial immune cells in the lungs. Published on January 17 in the Journal of Experimental Medicine, the study demonstrates how these alterations increase the susceptibility of cigarette smokers, as well as those exposed to second-hand and third-hand smoke, to respiratory infections and exacerbate inflammatory diseases such as chronic obstructive pulmonary disease (COPD).
COPD, a condition exacerbated by smoking, is the third leading cause of death globally. Smokers with COPD are particularly vulnerable to influenza infections, which can further deteriorate their condition by increasing airway inflammation and promoting the destruction of lung tissue. Despite the severity of COPD, there are currently no effective treatments available. Dr Wael Awad, from Monash University’s Biomedicine Discovery Institute and the lead author of the study, stated, “Until now, the mechanisms by which cigarette smoke skews immune responses and their connection to smoke-related diseases like COPD have been poorly understood.”
The study was collaboratively led by notable scientists, including Professor Jamie Rossjohn and Professor David P. Fairlie, alongside Professor Alexandra J. Corbett and Professor Philip M. Hansbro. The team focused on the effects of cigarette smoke on mucosal-associated invariant T (MAIT) cells, which are vital in fighting bacterial and viral infections and can promote either inflammation or tissue repair. MAIT cells are activated by a protein called MR1, found in almost every cell of the body and present bacterial chemicals on the surface of infected cells to initiate an immune response.
Professor David P. Fairlie commented on the broader implications of smoke exposure, “While we are aware of the significant health risks from various smoke sources, our knowledge about how specific smoke components affect the immune system and impact different parts of the human body is surprisingly limited.” The researchers used computer modelling to identify which components of cigarette smoke could be recognized by MR1, finding several molecules that not only bound to the protein but also altered its expression on the surface of cells. These chemicals, including benzaldehyde derivatives used in flavourings for cigarettes and e-cigarettes, blocked the activation of human MAIT cells by bacterial compounds.
Further investigations involved studying the effects of cigarette smoke on MAIT cells obtained from human blood and mice. The findings revealed a reduction in MAIT cell function when exposed to cigarette smoke. Mice repeatedly exposed to smoke developed symptoms of lung disease, which worsened when the mice were also infected with influenza. Long-term exposure to cigarette smoke was found to alter the protective functions of MAIT cells in mice, increasing their susceptibility to influenza infections and the likelihood of developing COPD.
Professor Philip M. Hansbro provided insights on the protective effects in mice lacking MAIT cells, “Mice devoid of MAIT cells were also protected from COPD induced by cigarette smoke, showing reduced levels of lung inflammation and no tissue deterioration in their lungs.” The collective findings underscore the importance of understanding the biological mechanisms by which cigarette smoke influences immune function and lung health. This study not only highlights the intricate nature of immune responses to cigarette smoke but also opens avenues for potential therapeutic strategies to treat COPD and other related lung diseases.
More information: Wael Awad et al, Cigarette smoke components modulate the MR1–MAIT axis, Journal of Experimental Medicine. DOI: 10.1084/jem.20240896
Journal information: Journal of Experimental Medicine Provided by Rockefeller University Press
