Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci.

Mahyar Aghapour, Christy B M Tulen, Mohsen Abdi Sarabi, Sönke Weinert, Mathias Müsken, Borna Relja, Frederik-Jan van Schooten, Andreas Jeron, Rüdiger Braun-Dullaeus, Alexander H Remels, Dunja Bruder

Journal: Cells 2022;11(11):1771

PMID: 35681466

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Plain Language Summary

Cigarette smoking can affect airway epithelial cells, causing overproduction of mucus, damage, and inflammation, which may result in the progression of airway diseases. Airway epithelial cells (AEC) rely on mitochondria for energy, and mitochondrial dysfunction may affect innate immunity and the integrity of the airway epithelium. Cigarette smoking is found to accelerate mitochondrial damage within AEC. Maintaining a normal microbial composition within the respiratory tract is essential for maintaining immunity. There is evidence that smoking cigarettes disrupts the microbial composition and increases the spread of pathogenic bacteria such as Streptococcus pneumoniae (Sp) which causes inflammation. By exposing 16HBE cells to Sp and cigarette smoke extract (CSE), this study investigated the effect of cigarette smoking on mitochondrial dysfunction in ACE in an in vitro model. Additionally, the study examined the direct and indirect pathways involved in cigarette smoking-induced mitochondrial dysfunction and altered innate immune response to Sp infection. CSE exposure decreases mitochondrial complex protein levels and mitochondrial membrane potential, which affects energy production. It also increases mitochondrial oxidative stress and mitochondrial degradation. All these factors lead to mitochondrial dysfunction in ACE. CSE exposure to ACE was associated with altered gene expression in the tight and adherence junctions that serve as a protective barrier against pathogens and pollutants and reduced type I interferon immune responses to Sp. Using the results of this study, healthcare professionals can gain a better understanding of the impact of cigarette smoking on mitochondrial dysfunction and how it increases susceptibility to Sp-related immune responses. It is necessary to conduct further studies to evaluate the effects of cigarette smoking on mitochondrial dysfunction, microbial composition disruption, and the interaction between AECs and elevated immune responses.

Abstract

Mitochondrial functionality is crucial for the execution of physiologic functions of metabolically active cells in the respiratory tract including airway epithelial cells (AECs). Cigarette smoke is known to impair mitochondrial function in AECs. However, the potential contribution of mitochondrial dysfunction in AECs to airway infection and airway epithelial barrier dysfunction is unknown. In this study, we used an in vitro model based on AECs exposed to cigarette smoke extract (CSE) followed by an infection with (). The levels of oxidative stress as an indicator of mitochondrial stress were quantified upon CSE and treatment. In addition, expression of proteins associated with mitophagy, mitochondrial content, and biogenesis as well as mitochondrial fission and fusion was quantified. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with indices of mitochondrial function. We observed that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to , particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to .

Address: Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke University, 39120 Magdeburg, Germany.; Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.; Department of Pharmacology and Toxicology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands.; Department of Internal Medicine/Cardiology and Angiology, Otto-von-Guericke University, 39120 Magdeburg, Germany.; Central Facility for Microscopy, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.; Experimental Radiology, Department of Radiology and Nuclear Medicine, 39120 Magdeburg, Germany.

DOI: 10.3390/cells11111771