Cigarette smoke-promoted acquisition of bacterial pathogens in the upper respiratory tract leads to enhanced inflammation in mice

Abstract

BackgroundBacterial colonization and recurrent infections of the respiratory tract contribute to the progression of chronic obstructive pulmonary disease (COPD). There is evidence that exacerbations of COPD are provoked by new bacterial strains acquired from the environment. Using a murine model of colonization, we examined whether chronic exposure to cigarette smoke (CS) promotes nasopharyngeal colonization with typical lung pathogens and whether colonization is linked to inflammation in the respiratory tract.MethodsC57BL/6 N mice were chronically exposed to CS. The upper airways of mice were colonized with nontypeable Haemophilus influenzae (NTHi) or Streptococcus pneumoniae. Bacterial colonization was determined in the upper respiratory tract and lung tissue. Inflammatory cells and cytokines were determined in lavage fluids. RT-PCR was performed for inflammatory mediators.ResultsChronic CS exposure resulted in significantly increased numbers of viable NTHi in the upper airways, whereas NTHi only marginally colonized air-exposed mice. Colonization with S. pneumoniae was enhanced in the upper respiratory tract of CS-exposed mice and was accompanied by increased translocation of S. pneumoniae into the lung. Bacterial colonization levels were associated with increased concentrations of inflammatory mediators and the number of immune cells in lavage fluids of the upper respiratory tract and the lung. Phagocytosis activity was reduced in whole blood granulocytes and monocytes of CS-exposed mice.ConclusionsThese findings demonstrate that exposure to CS impacts the ability of the host to control bacterial colonization of the upper airways, resulting in enhanced inflammation and susceptibility of the host to pathogens migrating into the lung.

Cigarette smoke and electronic cigarettes differentially activate bronchial epithelial cells

“…In the present study we did not observe a change in antimicrobial activity or barrier integrity after exposure of differentiated airway epithelium to ECIG-vapor. The results from the TCIG-exposed cells are in line with previous reports that TCIG-smoke leads to a defect in host defense and disruption of the epithelial barrier in vivo and in vitro [27,34,43]. We showed earlier that smoking is associated with reduced concentrations of hBD2 in airway secretions of patients with community acquired pneumonia, and that exposure of differentiated pHBE to volatile TCIG-smoke leads to a decreased expression and synthesis of hBD2 after infection with bacteria and an increased inflammatory reaction [27].…”

Cigarette smoke-induced disruption of pulmonary barrier and bacterial translocation drive tumor-associated inflammation and growth

“…Stable COPD patients are abundantly colonized with bacterial pathogens (e.g., NTHi, P. aeruginosa) and bacterial infections of the lung play an important role in the initiation of acute exacerbations of COPD (18,28). Bacterial colonization and infection of the lung contribute to the development of COPD by damaging epithelial surfaces and amplifying pulmonary inflammation (18,29,32). Moghaddam et al (17) demonstrated that pulmonary inflammation triggered by NTHi increases the growth of tumors in a K-ras-induced mouse model.…”

Cigarette Smoke Attenuates the Nasal Host Response to Streptococcus pneumoniae and Predisposes to Invasive Pneumococcal Disease in Mice

“…Importantly, we found smoking cessation post-nasal colonization fully rescued mice from mortality. This observation likely explains why nasal colonization with a clinical isolate of the same serotype (6A) did not cause IPD or attenuate nasal inflammation in a recent study by Voss et al (54), where mice did not continue to be exposed to smoke following colonization. These differences in experimental approach should be taken into consideration when investigating mechanisms of nasal pneumococcal colonization and IPD, especially given how quickly nasal CXCL-1 and CXCL-2 expression, as well as neutrophil recruitment, increased following smoking cessation in colonized mice.…”