title: Combined exposure to bacteria and cigarette smoke resembles characteristic phenotypes of human COPD in a murine disease model.
abstract: Abundant microbial colonization is a hallmark of COPD and smoke exposure likely increases the susceptibility to colonization and infection. The aim of the present study was to characterize the pulmonary changes of a combined exposure to cigarette smoke (CS) and microbial challenge in a preclinical murine COPD model. Animals were exposed to CS for 2 weeks, 3, and 6 months. Low and high doses of heat inactivated nontypeable Haemophilus influenzae (NTHi) were administered by inhalation during the whole exposure time. Pulmonary changes were analyzed by stereology, pulmonary function tests, measurements of inflammatory cells and mediators, and histopathology. Exposure of smoke in a relatively low concentration caused COPD-like changes of pulmonary function and only little inflammation. The coadministration of low dose NTHi (ld-NTHi) augmented a macrophage dominated inflammatory profile, while high dose NTHi (hd-NTHi) induced a neutrophilic inflammatory pattern. IL-17A secretion was solely dependent on the exposure to NTHi. Also goblet cell metaplasia and the formation of lymphoid aggregates depended on exposure to bacteria. In conclusion, the combination of exposure to smoke and bacterial compounds resulted in a mouse model that resembles several aspects of human disease. Exposure to microbial structural components appears necessary to model important pathologic features of the disease and the quantity of the exposure with microorganisms has a strong effect on the phenotype.
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany. Electronic address: Christian.herr@uks.eu.
authors.forename: Christian
authors.initials: C
authors.lastname: Herr
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany.
authors.forename: Gang
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Anatomy, Saarland University Hospital, 66424 Homburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tschernig
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany; Department of Experimental Pulmonology, Saarland University Hospital, 66424 Homburg, Germany.
authors.forename: Quoc Thai
authors.initials: QT
authors.lastname: Dinh
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Beißwenger
authors.affiliation: Department of Internal Medicine V-Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006192:Haemophilus Infections / Q000150:complications*; D006193:Haemophilus influenzae; D006801:Humans; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000382:microbiology* / Q000473:pathology*; D012906:Smoke; D014026:Nicotiana
chemical_list: D012906:Smoke
keywords: Bacteria; Chronic obstructive pulmonary disease; Emphysema; IL-17; Inflammation; iBALT