title: Allergic airway inflammation inhibits pulmonary antibacterial host defense.
abstract: The innate immune system of the lung is a multicomponent host defense system and in addition has an instructing role in regulating the quality and quantity of the adaptive immune response. When the interaction between innate and adaptive immunity is disturbed, pathological conditions such as asthma can develop. It was the aim of the study to investigate the effect of the allergic inflammation of the lung on the innate host defense during bacterial infection. Human bronchial epithelial cells were preincubated with Th2 cytokines and infected with Pseudomonas aeruginosa. The effect of the Th2 cytokines on the mRNA levels of antimicrobial peptides and the antimicrobial activity of HBEC was determined. To investigate the influence of an allergic inflammation on pulmonary host defense in vivo, mice sensitized and challenged with OVA were infected with P. aeruginosa, and the number of viable bacteria in the lungs was determined together with markers of inflammation like cytokines and antimicrobial peptides. Exposure of airway epithelial cells to Th2 cytokines resulted in a significantly decreased antimicrobial activity of the cells and in suppressed mRNA levels of the antimicrobial peptide human beta-defensin 2. Furthermore, mice with allergic airway inflammation had significantly more viable bacteria in their lungs after infection. This was consistent with reduced levels of proinflammatory cytokines and of the antimicrobial peptide cathelin-related antimicrobial peptide. These results show that an allergic airway inflammation suppresses the innate antimicrobial host defense. The adaptive immune system modulates the functions of the pulmonary innate immune system.
authors.affiliation: Department of Internal Medicine, Division for Pulmonary Diseases, Philipps-Universität Marburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Beisswenger
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kandler
authors.forename: Christian
authors.initials: C
authors.lastname: Hess
authors.forename: Holger
authors.initials: H
authors.lastname: Garn
authors.forename: Kerstin
authors.initials: K
authors.lastname: Felgentreff
authors.forename: Michael
authors.initials: M
authors.lastname: Wegmann
authors.forename: Harald
authors.initials: H
authors.lastname: Renz
authors.forename: Claus
authors.initials: C
authors.lastname: Vogelmeier
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D002460:Cell Line; D016207:Cytokines / Q000502:physiology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D000485:Allergens; D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D010047:Ovalbumin