Toll-Like Receptor 2 Modulates Pulmonary Inflammation and TNF-a Release Mediated by Mycoplasma pneumoniae

Objectives: To investigate the roles that Toll-like receptors (TLRs) play in lung inflammation mediated by Mycoplasma pneumoniae (MP).& nbsp;Methods: The changes in TLRs and tumor necrosis factor alpha (TNF-alpha) in peripheral blood of children with M. pneumoniae pneumonia (MPP) were monitored, and the interactions of signaling molecules regulating TNF-alpha release in A549 cells and neutrophils after M. pneumoniae stimulation were investigated. In TLR2 knockout (TLR2-/-) mice, the levels of TNF-alpha in bronchial alveolar lavage fluid (BALF) and peripheral blood after mycoplasma infection and the pathological changes in the lung tissue of mice were detected.& nbsp;Results: TNF-alpha levels in peripheral blood of children with MPP were higher than those in non-infected children, and children with refractory MPP had the highest levels of TNF-alpha and TLR2. TNF-alpha secretion and TLR2, myeloid differentiation primary response 88 (MyD88) and phospho-p65(p-p65) levels were increased in stimulated cells. TNF-alpha secretion was suppressed upon siRNA-mediated TLR2 silencing. Pharmacological inhibition of nuclear factor-kappa B (NF-kappa B) and MyD88 effectively reduced TNF-alpha expression. Compared with wild-type mice, the TNF-alpha in serum and BALF decreased, and lung pro-inflammatory response was partially suppressed in TLR2-/- mice.& nbsp;Conclusion: We concluded that TLR2 regulates M. pneumoniae-mediated lung inflammation and TNF-alpha release through the TLR2-MyD88-NF-kappa B signaling pathway.