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

Abstract

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.

Clinical efficacy of budesonide combined with acetylcysteine in the treatment of mycoplasma pneumonia infection

“…Damage to alveolar epithelium during pulmonary MP infection leads to the activation of alveolar macrophages. 27 Indeed, when activated, immune cells including macrophages and lymphocytes play a crucial role in inflammatory responses through the release of various endogenous mediators such as pro-inflammatory prostaglandins. TNF-α and IL-6 are two well-known proinflammatory cytokines that are thought to be central mediators in the cytokine cascades, and also important cytokines for immune and inflammatory response.…”

“…Damage to alveolar epithelium during pulmonary MP infection leads to the activation of alveolar macrophages 27 . Indeed, when activated, immune cells including macrophages and lymphocytes play a crucial role in inflammatory responses through the release of various endogenous mediators such as pro‐inflammatory prostaglandins.…”

Conserved Domains in Variable Surface Lipoproteins A-G of Mycoplasma hyorhinis May Serve as Probable Multi-Epitope Candidate Vaccine: Computational Reverse Vaccinology Approach

“…Moreover, many Mycoplasma sp. trigger an immune response via TLR2 receptors [ 49 , 50 , 51 ]. The involvement of TLR2 receptors in immune stimulation can be assessed by assessing the upregulation of interferons and a specific set of cytokines and immune regulatory factors such as NF-κB [ 52 ].…”

The role of inflammation in hematopoiesis and bone marrow failure: What can we learn from mouse models?

“…Besides their well-known job in effector immune cells, TLRs influence HSCs in terms of proliferation and differentiation in response to ‘danger’ signals (e.g. various infections, as well as purified or synthetic TLR ligands induce the release of proinflammatory cytokines like TNF) ( 92 ), helping the hematopoietic system to recognize stress events and inducing emergency hematopoiesis ( 87 , 93 , 94 ). Hence, the immuno-surveillance effects of TLRs expressed on HSCs induce the activation of quiescent HSCs pushing them to proliferate and differentiate into myeloid cells.…”