title: A deficient TLR2 signaling promotes airway mucin production in Mycoplasma pneumoniae-infected allergic mice.
abstract: The original hygiene hypothesis suggests that early childhood respiratory infections preceding allergen exposure may decrease the prevalence of allergic diseases. We have recently demonstrated that Mycoplasma pneumoniae infection preceding allergen exposure reduced allergic responses in mice. However, the molecular mechanisms underlying the protective role of M. pneumoniae in allergic responses, particularly airway mucin production, remain unclear. Wild-type and Toll-like receptor 2 (TLR2)-deficient mice with a respiratory M. pneumoniae infection preceding allergen (ovalbumin) challenge were utilized to determine the regulatory role of TLR2-IFN-gamma signaling pathway in airway mucin expression. Furthermore, air-liquid interface cultures of mouse primary tracheal epithelial cells were performed to examine the effects of IFN-gamma on mucin expression. In wild-type mice, M. pneumoniae infection preceding allergen challenge significantly reduced airway mucins but increased IFN-gamma. In sharp contrast, in TLR2-deficient mice, M. pneumoniae preceding allergen challenge resulted in increased mucin protein without a noticeable change of IFN-gamma. In cultured mouse primary tracheal epithelial cells, IFN-gamma was shown to directly inhibit mucin expression in a dose-dependent manner. Our study demonstrates for the first time that a respiratory M. pneumoniae infection preceding allergen challenge reduces airway epithelial mucin expression in part through TLR2-IFN-gamma signaling pathway. A bacterial infection in asthmatic subjects with weakened TLR2-IFN-gamma signaling may result in an exaggerated airway mucin production.
authors.affiliation: Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: John G
authors.initials: JG
authors.lastname: Rino
authors.forename: Samithamby
authors.initials: S
authors.lastname: Jeyaseelan
authors.forename: Rachel
authors.initials: R
authors.lastname: Breed
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
mesh_terms: D000485:Allergens; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006967:Hypersensitivity; D007371:Interferon-gamma / Q000235:genetics; D051379:Mice; D055271:Mucin 5AC; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics; D009177:Mycoplasma pneumoniae; D011019:Pneumonia, Mycoplasma / Q000276:immunology* / Q000503:physiopathology*; D011401:Promoter Regions, Genetic; D020545:Respiratory Mucosa / Q000276:immunology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014132:Trachea
chemical_list: D000485:Allergens; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D007371:Interferon-gamma