TLR2 signaling is critical for Mycoplasma pneumoniae-induced airway mucin expression.
Excessive airway mucin production contributes to airway obstruction in lung diseases such as asthma and chronic obstructive pulmonary disease. Respiratory infections, such as atypical bacterium Mycoplasma pneumoniae (Mp), have been proposed to worsen asthma and chronic obstructive pulmonary disease in part through increasing mucin. However, the molecular mechanisms involved in infection-induced airway mucin overexpression remain to be determined. TLRs have been recently shown to be a critical component in host innate immune response to infections. TLR2 signaling has been proposed to be involved in inflammatory cell activation by mycoplasma-derived lipoproteins. In this study, we show that TLR2 signaling is critical in Mp-induced airway mucin expression in mice and human lung epithelial cells. Respiratory Mp infection in BALB/c mice activated TLR2 signaling and increased airway mucin. A TLR2-neutralizing Ab significantly reduced mucin expression in Mp-infected BALB/c mice. Furthermore, Mp-induced airway mucin was abolished in TLR2 gene-deficient C57BL/6 mice. Additionally, Mp was shown to increase human lung A549 epithelial cell mucin expression, which was inhibited by the overexpression of a human TLR2 dominant-negative mutant. These results clearly demonstrate that respiratory Mp infection increases airway mucin expression, which is dependent on the activation of TLR2 signaling.
Chu
Hong Wei
HW
Department of Medicine, National Jewish Medical and Research Center and University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Jeyaseelan
Samithamby
S
Rino
John G
JG
Voelker
Dennis R
DR
Wexler
Rachel B
RB
Campbell
Krista
K
Harbeck
Ronald J
RJ
Martin
Richard J
RJ
D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000302:isolation & purification; D045744:Cell Line, Tumor; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D008074:Lipoproteins / Q000276:immunology / Q000302:isolation & purification; D008168:Lung / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000096:biosynthesis*; D009177:Mycoplasma pneumoniae / Q000737:chemistry / Q000276:immunology*; D011019:Pneumonia, Mycoplasma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051195:Toll-Like Receptor 2; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D001426:Bacterial Proteins; D007106:Immune Sera; D008074:Lipoproteins; D009077:Mucins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2