Interaction between cigarette smoke and mycoplasma infection: a murine model.

Cigarette smoke has a major impact on health issues worldwide. Although genetics certainly is a factor in the sensitivity to cigarette smoke, other lung environmental factors, such as infection, potentially could interact with cigarette smoke to induce inflammatory changes associated with various diseases. Four groups of BALB/c mice (smoking only; smoking + M. pneumoniae infection; mycoplasma only; saline control) were studied for eight weeks to determine the interactive outcomes of inflammation and structural changes in the smoking plus mycoplasma group. This group did have significantly higher amounts of neutrophil degranulation in the outer airway wall area (smooth muscle to alveolar attachments) (p = 0.03) and mRNA expression of matrix metalloproteinase-9 (p= 0.045). Although there was not a significant difference in alveolar tissue elastin between the groups, the smoking plus mycoplasma group had a level approximately 20% below the other groups. Even in this relatively short duration study, it appears that an infectious process can interact with cigarette smoke to produce a destructive type of inflammatory response (activated neutrophils and metalloproteinase-9) seen in the outer airway wall area.

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.

Mycoplasma pneumoniae infection increases airway collagen deposition in a murine model of allergic airway inflammation.

Mycoplasma pneumoniae (Mp) has been linked to chronic asthma. Airway remodeling (e.g., airway collagen deposition or fibrosis) is one of the pathological features of chronic asthma. However, the effects of respiratory Mp infection on airway fibrosis in asthma remain unclear. In the present study, we hypothesized that respiratory Mp infection may increase the airway collagen deposition in a murine model of allergic airway inflammation in part through upregulation of transforming growth factor (TGF)-beta1. Double (2 wk apart) inoculations of Mp or saline (control) were given to mice with or without previous allergen (ovalbumin) challenges. On days 14 and 42 after the last Mp or saline, lung tissue and bronchoalveolar lavage (BAL) fluid were collected for analyses of collagen and TGF-beta1 at protein and mRNA levels. In allergen-naïve mice, Mp did not alter airway wall collagen. In allergen-challenged mice, Mp infections did not change airway wall collagen deposition on day 14 but increased the airway collagen on day 42; this increase was accompanied by increased TGF-beta1 protein in the airway wall and reduced TGF-beta1 protein release from the lung tissue into BAL fluid. Our results suggest that Mp infections could modulate airway collagen deposition in a murine model of allergic airway inflammation with TGF-beta1 involved in the collagen deposition process.