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

Sci Rep. 2016 Feb 10:6:20609. doi: 10.1038/srep20609.

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.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Adolescent
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Cell Proliferation / drug effects
  • Child
  • Child, Preschool
  • Cysteine / metabolism
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • Female
  • Humans
  • Infant
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism
  • Leukotrienes / metabolism
  • Male
  • Microscopy, Fluorescence
  • Myeloid Differentiation Factor 88 / metabolism
  • Neutrophils / cytology
  • Neutrophils / immunology
  • Odds Ratio
  • Palatine Tonsil / microbiology*
  • Palatine Tonsil / pathology
  • Palatine Tonsil / surgery
  • Real-Time Polymerase Chain Reaction
  • Sleep Apnea, Obstructive / etiology*
  • Streptococcal Infections / complications*
  • Streptococcal Infections / microbiology
  • Streptococcus pyogenes / genetics
  • Streptococcus pyogenes / isolation & purification
  • Streptococcus pyogenes / metabolism*
  • Streptolysins / genetics
  • Streptolysins / metabolism
  • Toll-Like Receptor 4 / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Adaptor Proteins, Vesicular Transport
  • Bacterial Proteins
  • DNA, Bacterial
  • Leukotrienes
  • Myeloid Differentiation Factor 88
  • Streptolysins
  • TICAM1 protein, human
  • Toll-Like Receptor 4
  • cysteinyl-leukotriene
  • streptolysin O
  • p38 Mitogen-Activated Protein Kinases
  • Cysteine