Frontiers in Cellular and Infection Microbiology (Mar 2022)

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

  • Ming Chen,
  • Ming Chen,
  • Huan Deng,
  • Yue Zhao,
  • Xueqing Miao,
  • Haiyan Gu,
  • Ying Bi,
  • Yifan Zhu,
  • Yun Guo,
  • Shuang Shi,
  • Jiejing Xu,
  • Deyu Zhao,
  • Feng Liu

DOI
https://doi.org/10.3389/fcimb.2022.824027
Journal volume & issue
Vol. 12

Abstract

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

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