title: Cigarette smoke-promoted acquisition of bacterial pathogens in the upper respiratory tract leads to enhanced inflammation in mice.
abstract: BACKGROUND
  Bacterial 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.
  
  
  METHODS
  C57BL/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.
  
  
  RESULTS
  Chronic 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, 66421, Homburg/Saar, Germany. Meike.Voss@uks.eu.
authors.forename: Meike
authors.initials: M
authors.lastname: Voss
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, 66421, Homburg/Saar, Germany. bodo-wonnenberg@gmx.de.
authors.forename: Bodo
authors.initials: B
authors.lastname: Wonnenberg
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, 66421, Homburg/Saar, Germany. Anja.Honecker@uks.eu.
authors.forename: Anja
authors.initials: A
authors.lastname: Honecker
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, 66421, Homburg/Saar, Germany. Andreas.Kamyschnikow@uks.eu.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kamyschnikow
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, 66421, Homburg/Saar, Germany. Christian.Herr@uks.eu.
authors.forename: Christian
authors.initials: C
authors.lastname: Herr
authors.affiliation: Institute of Medical Microbiology and Hygiene, Saarland University, 66421, Homburg/Saar, Germany. Markus.Bischoff@uks.eu.
authors.forename: Markus
authors.initials: M
authors.lastname: Bischoff
authors.affiliation: Institute of Anatomy and Cell Biology, Saarland University, 66421, Homburg/Saar, Germany. Thomas.Tschernig@uks.eu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tschernig
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, 66421, Homburg/Saar, Germany. Robert.Bals@uks.eu.
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, 66421, Homburg/Saar, Germany. christoph.beisswenger@uks.eu.
authors.forename: Christoph
authors.initials: C
authors.lastname: Beisswenger
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D006192:Haemophilus Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000276:immunology / Q000472:pathogenicity*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D011018:Pneumonia, Pneumococcal / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D012906:Smoke / Q000009:adverse effects; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012906:Smoke; D014028:Tobacco Smoke Pollution