A deficient TLR2 signaling promotes airway mucin production in Mycoplasma pneumoniae-infected allergic mice

Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado Submitted 8 August 2006 ; accepted in final form 24 December 2006 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- 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- on mucin expression. In wild-type mice, M. pneumoniae infection preceding allergen challenge significantly reduced airway mucins but increased IFN- . In sharp contrast, in TLR2-deficient mice, M. pneumoniae preceding allergen challenge resulted in increased mucin protein without a noticeable change of IFN- . In cultured mouse primary tracheal epithelial cells, IFN- 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- signaling pathway. A bacterial infection in asthmatic subjects with weakened TLR2-IFN- signaling may result in an exaggerated airway mucin production. asthma; mucus; interferon- ; Toll-like receptor 2 Address for reprint requests and other correspondence: H. W. Chu, Dept. of Medicine, National Jewish Medical and Research Center, 1400 Jackson St., Rm. D104, Denver, CO 80206 (e-mail: chuhw{at}njc.org )