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

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.

Group A streptococcal pharyngitis: Immune responses involved in bacterial clearance and GAS-associated immunopathologies

“…8 The composition of immune cells in tonsils from recurrent GAS tonsillitis patients and from tonsillar hypertrophy patients is similar, and upon stimulation with GAS, both produce a Th1 cytokine response. 136,147 A study by Viciani et al 177 reported an association between OSAS and GAS tonsil colonization. These authors showed that the GAS toxin SLO induced production of CysLTs by a TLR4-mediated pathway that involved the TLR adaptors MyD88 and Toll/IL-1R domain-containing adapter-inducing IFN-and p38 MAPK.…”

“…GAS pharyngitis is associated with pediatric adenotonsillar hypertrophy (abnormal enlargement of the tonsil) and has recently been implicated in pediatric OSAS, which is primarily characterized by enlarged tonsils. 177 Tonsillar hypertrophy is caused by the proliferation of immune cells in the follicles and interfollicular areas of the tonsils in response to infection, and GAS was present in the tonsillar-reticulated crypt epithelium of 37% of children who had tonsillectomy for adenotonsillar hypertrophy. 8 The composition of immune cells in tonsils from recurrent GAS tonsillitis patients and from tonsillar hypertrophy patients is similar, and upon stimulation with GAS, both produce a Th1 cytokine response.…”

The Group A Streptococcus M1​​​​​​​T1 clone post-transcriptionally modifies innate immune signalling to promote infection

“…reported an association between OSAS and GAS tonsil colonisation. These authors showed that the GAS toxin SLO induced production of CysLTs, by a TLR4-mediated pathway, that involved the TLR adaptors MyD88 and TRIF and the p38 MAP kinase (130). CysLTs activated primary T and B cell proliferation in vitro, which might mediate the development of tonsil hypertrophy, and thus paediatric OSAS.…”

“…GAS pharyngitis is associated with paediatric adenotonsillar hypertrophy (abnormal enlargement of the tonsil) and has recently been implicated in paediatric obstructive sleep apnoea syndrome (OSAS), which is primarily characterised by enlarged tonsils (130). Tonsillar hypertrophy is caused by the proliferation of immune cells in the follicles and interfollicular areas of the tonsils in response to infection, and GAS was present in the tonsillar reticulated crypt epithelium of 37 % of children who had tonsillectomy for adenotonsillar hypertrophy (48).…”

“…Streptococcus pyogenes (Group A Streptococcus; GAS) is the most common bacterial cause of acute pharyngitis(92), with over 616 million incident cases of GAS pharyngitis predicted to occur worldwide each year(93). GAS pharyngitis has also been associated with inflammatory complications such as scarlet fever(250), chronic diseases including tonsillar hypertrophy and sleep apnoea(130), and the post-infectious sequelae including acute rheumatic fever(254), poststreptococcal glomerulonephritis (300) and guttate psoriasis (301). During pharyngitis, GAS colonises the mucosal layers of the pharynx including the palatine tonsil epithelium, forming biofilms on the tonsillar surface and inside tonsillar crypts, as well as invading the epithelium to survive intracellularly (48, 50).…”