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With flu season around the corner, and coronavirus cases showing no evidence of ceasing, vulnerable people will be trying their best to limit the risk of becoming ill this winter. Amongst the vulnerable are those with chronic obstructive pulmonary disease (COPD), which is a progressive lung disease, characterised by limitations in airflow and alveolar destruction [1]. Certain environments and lifestyle choices are responsible for exacerbation of potential COPD development, such as fumes, air pollution, and most commonly, smoking [2]. Increased awareness of the implications of smoking has encouraged people to quit, so much so, that incidences in the UK has decreased by a substantial amount since the 1940s, where 82% of men were smokers [3]. Nevertheless, despite this decline, cigarette smoking is one of the leading causes of fatalities and is responsible for increasing the risk of viral illnesses in those with COPD [1].
After infection by a virus, viral peptide fragments bind to major histocompatibility complex (MHC) class I molecules on our cell surface, and then these peptide fragments are displayed for recognition by cytotoxic CD8+ T-cells [1]. The protein complex responsible for generating these peptides for antigen presentation are immunoproteasomes, which are made up of inducible catalytic subunits, including low molecular weight protein (LMP) 2 and 7 and multicatalytic endopeptidase complex (MECL) 1 subunit [1]. Previous research has highlighted the importance of these subunits and the key role they play in generating antigenic MHC class I eptiopes during a viral infection, in that if there is absence of any of the subunits, then antiviral activity is severely limited [1]. Earlier this year, a paper by Chen et al. was published investigating the effect of cigarette smoke on induction of immunoproteasomes and MHC class I presentation after viral infection [1]. Cigarette smoke was found to significantly inhibit the induction of the catalytic subunits of the immunoproteasome; even doses as low as 10% inhibited induction of MECL-1 [1]. After infecting a human cell line with either influenza A virus (IAV) or human rhinovirus, they conducted smoke exposure experiments and found IVA-mediated induction of the immunoproteasome was severally disrupted and reduced MHC class I surface expression [1]. In addition, viral CD8+ T-cell activation also diminished after cigarette smoke exposure [1]. Blood samples were taken from COPD patients and the number of CD3+ CD8+ IAV-tetramer+ T-cells present was lower compared to lung-healthy controls providing further evidence from that the antiviral adaptive immune response is impaired in smokers and COPD patients [1].
Altered MHC class I antigen presentation in COPD disease exacerbation is majorly understudied, so this area of research is an increasing area of interest for scientists [1]. It would be hoped that results of this kind will prompt smokers with respiratory diseases, like COPD, to consider the risk-reward battle and encourage them to quit or at least reduce smoking.
Want to read more about immunology? Check out the ‘Immunology’ section of our published paper database.
Written by DWS Microbiologist Kirsty McTear
References
- Wang Y, Chen J, Wang X, Schmalen A, Haines S, Wolff M, et al. Antiviral CD8+ T cell immune responses are impaired by cigarette smoke and in COPD. 0302 - Airway cell biology and immunopathology. 2023; doi:10.1183/23120541.lsc-2023.179
- NHS. Causes - Chronic obstructive pulmonary disease (COPD) [Internet]. NHS; 2023 [cited 2023 Nov 7]. Available from: https://www.nhs.uk/conditions/chronic-obstructive-pulmonary-disease-copd/causes/
- Action on Smoke and Health (ASH). Smoking statistics [Internet]. 2023 [cited 2023 Nov 7]. Available from: https://ash.org.uk/uploads/Smoking-Statistics-Fact-Sheet.pdf?v=1697728811
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