Abstract
Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of primary human nasal epithelial cells (PHNECs). Compared to non-CS-exposed individuals, PHNEC from in vivo CS-exposed individuals secreted less chemokine ligand (C-C motif) 20 (CCL20), Beta-defensin 1 (BD-1), and SLPI apically, less BD-1 and SLPI basolaterally, and more CCL20 basolaterally. Cigarette smoke extract (CSE) exposure in vitro decreased the apical secretion of CCL20 and beta-defensin 1 by PHNEC from non-CS-exposed individuals. Exposing PHNEC from non-CS exposed to CSE also significantly decreased the levels of many mRNA transcripts that are involved in immune signaling. Our results show that in vivo or in vitro exposure to CS alters the secretion of key antimicrobial peptides from PHNEC, but that in vivo CS exposure is a much more important modifier of antimicrobial peptide secretion. Based on the gene expression data, it appears that CSE disrupts multiple immune signaling pathways in PHNEC. Our results provide mechanistic insight into how CS exposure alters the innate immune response and increases an individual’s susceptibility to pathogen infection.
Highlights
There is copious evidence that exposure to primary cigarette smoke (CL) and/or secondhand cigarette smoke (SHCS) is associated with increased frequency of infections or other symptoms of perturbations of the immune system
Subsequent studies of human monocytes exposed to bacterial toxins and to cigarette smoke extract (CSE) demonstrated extremely aberrant immune responses relative to cells exposed to bacterial toxins but not exposed to CSE [17]
Beta-defensin 1 (BD1), secretory leukocyte protease inhibitor (SLPI), and CCL20 were assayed by ELISA in apical and basolateral secretions either using commercially prepared assay kits or ELISAs developed from ELISA development kits
Summary
There is copious evidence that exposure to primary cigarette smoke (CL) and/or secondhand cigarette smoke (SHCS) is associated with increased frequency of infections or other symptoms of perturbations of the immune system. Exposure to primary CL or SHCS is a risk factor for recurrent otitis media, upper respiratory tract infection [1, 2], meningococcal. Upper airways of CS-exposed individuals harbor more potential pathogens than those of non-smokers [14]. These findings are consistent with studies in mice. In studies looking at changes in immune responses to bacterial challenge in mice exposed to nicotine, exposed mice exhibited significantly higher titers of influenza virus following infection [16]. Subsequent studies of human monocytes exposed to bacterial toxins and to cigarette smoke extract (CSE) demonstrated extremely aberrant immune responses relative to cells exposed to bacterial toxins but not exposed to CSE [17]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
