Viciani Elisa, Montagnani Francesca, Tavarini Simona, Tordini Giacinta, Maccari Silvia, Morandi Matteo, Faenzi Elisa, Biagini Cesare, Romano Antonio, Salerni Lorenzo, Finco Oretta, Lazzi Stefano, Ruggiero Paolo, De Luca Andrea, Barocchi Michèle A, Manetti Andrea G O
GSK Vaccines S.r.l., Via Fiorentina, 1 53100 Siena, Italy.
Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy.
Sci Rep. 2016 Feb 10;6:20609. doi: 10.1038/srep20609.
The involvement of pathogenic bacteria in obstructive sleep apnoea syndrome (OSAS) has yet to be elucidated. We investigated the possible role of group A streptococcus (GAS) in OSAS pathogenesis. In 40 tonsillectomized patients affected by OSAS and 80 healthy controls, significant (p < 0.0001) association of GAS with paediatric OSAS was found. Supernatant from streptolysin O (SLO)-producing GAS induced production of cysteinyl leukotrienes (CysLTs) in tonsil mononuclear cells (TMCs). CysLTs-treated TMCs showed significant (p < 0.05) proliferation of CD4+ T, CD19+ and CD19+CD27+CD38+ B lymphocytes. We discovered a SLO-dependent activation of CysLTs production through a pathway involving TOLL-like receptor 4 (TLR4), TIR-domain-containing adapter-inducing interferon-β (TRIF), Myeloid differentiation primary response gene 88 (MyD88), and p38 MAP Kinase. In conclusion, we hypothesise that GAS may contribute to paediatric tonsillar hyperplasia through CysLTs production induced by SLO, and this might explain its association with OSAS.
病原菌在阻塞性睡眠呼吸暂停综合征(OSAS)中的作用尚未阐明。我们研究了A组链球菌(GAS)在OSAS发病机制中的可能作用。在40例受OSAS影响的扁桃体切除患者和80例健康对照中,发现GAS与儿童OSAS存在显著(p < 0.0001)关联。产生链球菌溶血素O(SLO)的GAS的上清液可诱导扁桃体单核细胞(TMC)产生半胱氨酰白三烯(CysLTs)。经CysLTs处理的TMC显示CD4 + T、CD19 +和CD19 + CD27 + CD38 + B淋巴细胞有显著(p < 0.05)增殖。我们发现通过涉及Toll样受体4(TLR4)、含TIR结构域的接头诱导干扰素-β(TRIF)、髓样分化初级反应基因88(MyD88)和p38丝裂原活化蛋白激酶的途径,SLO可依赖性激活CysLTs的产生。总之,我们推测GAS可能通过SLO诱导产生CysLTs导致儿童扁桃体增生,这可能解释了其与OSAS的关联。