Impact of Cigarette Smoke on Clearance and Inflammation after Pseudomonas aeruginosa Infection

Abstract

The object of this study was to investigate the impact of cigarette smoke on bacterial clearance and immune inflammatory parameters after infection with Pseudomonas aeruginosa in mice. We observed a delayed rate of bacterial clearance in smoke-exposed compared with sham-exposed mice. This was associated with increased inflammation characterized by greater numbers of neutrophils and mononuclear cells in the bronchoalveolar lavage. After infection, we observed increased levels of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) and chemokines (monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-2 [MIP-2]) as well as myeloperoxidase and proteolytic activity in the lungs of smoke-exposed compared with sham-exposed animals. Delayed clearance was associated with increased morbidity and greater weight loss of smoke-exposed mice. After delivery of inactivated bacteria, we observed a similar inflammatory response, clinical score, and tumor necrosis factor-alpha expression in smoke- and sham-exposed animals, suggesting that increased inflammation and altered clinical presentation are due to the delayed rate of bacterial clearance. Our findings suggest that cigarette smoke affects respiratory immune-inflammatory responses elicited by bacteria. We postulate that altered respiratory host defense may be implicated in smoking-related diseases such as chronic obstructive pulmonary disease.

Cigarette Smoke Impairs NK Cell-Dependent Tumor Immune Surveillance

“…We have previously reported on changes in the immune status in these animals. Cigarette smoke exposure decreases dendritic cell numbers in the lungs and impairs immune responses against viral and bacterial agents (18,26). These immunological changes precede the formation of emphysematous lesions that are observed following 4 -6 mo of cigarette smoke exposure (27).…”

Suppression of pulmonary innate host defense in smokers

“…Also animal experiments showed that smoke exposure results in decreased host defense of the lung. Cigarette smoke applied to mice for 6-8 weeks resulted in a delayed rate of bacterial clearance as compared to sham-exposed animals 4 . Smoke decreases the function of the mucociliary clearance 5 , promotes adhesion of bacteria to the airway epithelia 6 , and affects the function of pulmonary host defense cells 7 .…”

“…It is known that smoking alters the function of host defense components of the lung. Smoke exposed animals also reveal increased inflammation but delayed clearance of Pseudomonas aeruginosa after infection 4 . In addition, host defenses against respiratory syncytial virus appear suppressed after smoke exposure 24 .…”

Experimental Therapeutics of Nrf2 as a Target for Prevention of Bacterial Exacerbations in COPD

“…Impairment of bacterial phagocytosis by alveolar macrophages may result in chronic bacterial colonization. Results of studies in mouse models indicate that chronic cigarette smoke exposure impairs bacterial phagocytosis by alveolar macrophages and diminishes pulmonary bacterial clearance (17)(18)(19). The underlying mechanism for this defect is not well understood.…”