Paediatric obstructive sleep apnoea syndrome (OSAS) is associated with tonsil colonisation by Streptococcus pyogenes

Elisa Viciani,Cesare Biagini,Giacinta Tordini,Simona Tavarini,Stefano Lazzi,Michèle A Barocchi,Andrea De Luca,Lorenzo Salerni,Francesca Montagnani,Andrea G O Manetti,Silvia Maccari,Paolo Ruggiero,Matteo Morandi,Antonio Romano,Elisa Faenzi,Oretta Finco

doi:10.1038/srep20609

Elisa Viciani, Cesare Biagini + Show 14 more

Open Access

https://doi.org/10.1038/srep20609

Copy DOI

Abstract

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.

Highlights

The involvement of pathogenic bacteria in obstructive sleep apnoea syndrome (OSAS) has yet to be elucidated
In the exclusively paediatric OSAS group, we found that group A streptococcus (GAS) was the pathogen most significantly associated with OSAS (OR = 7.14, 95% CI 2.81–18.10, p < 0.0001), H. influenzae and S. pneumoniae showed an association, but with a wider confidence interval (Table 2)
Reports indicate that production of Cysteinyl leukotrienes (CysLTs) increases in the tonsils of paediatric OSAS9,17, and it is known that GAS streptolysin O (SLO) induces production of CysLTs in human granulocytes[22]

Summary

Introduction

The involvement of pathogenic bacteria in obstructive sleep apnoea syndrome (OSAS) has yet to be elucidated. Supernatant from streptolysin O (SLO)-producing GAS induced production of cysteinyl leukotrienes (CysLTs) in tonsil mononuclear cells (TMCs). 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. We hypothesise that GAS may contribute to paediatric tonsillar hyperplasia through CysLTs production induced by SLO, and this might explain its association with OSAS. Despite the use of antibiotics, adenotonsillectomy is commonly indicated to treat certain tonsil diseases[1,2,3,4]. Tonsillectomy has been routinely applied to treat recurrent tonsillitis (RT); more recently, obstructive sleep apnoea syndrome (OSAS) has emerged in children, as the primary indication for surgical removal of adenoids and tonsils[1,5,6]. SLO activates toll like receptor 4 (TLR4)[23], whose signalling pattern regulates the activation of cytosolic phospholipase A2 (cPLA2) in LPS-activated murine macrophages[24]

Objectives

Methods

Results

Conclusion