How Cigarette Smoke Weakens Lung Immune Cells: Study Finds
A new study showed 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. The findings are published in the Journal of Experimental Medicine (JEM), 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).
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.
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.
Reference: Wael Awad, Jemma R. Mayall, Weijun Xu, Matt D. Johansen, Timothy Patton, Xin Yi Lim, Izabela Galvao, Lauren J. Howson, Alexandra C. Brown, Tatt Jhong Haw, Chantal Donovan, Shatarupa Das, Gesa J. Albers, Tsung-Yu Pai, Elinor Hortle, Caitlin M. Gillis, Nicole G. Hansbro, Jay C. Horvat, Ligong Liu, Jeffrey Y.W. Mak, James McCluskey, David P. Fairlie, Alexandra J. Corbett, Philip M. Hansbro, Jamie Rossjohn; Cigarette smoke components modulate the MR1–MAIT axis. J Exp Med 3 February 2025; 222 (2): e20240896. doi: https://doi.org/10.1084/jem.20240896
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