title: 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.
authors: GSK Vaccines S.r.l., Via Fiorentina, 1 53100 Siena, Italy.
authors: Elisa
authors: E
authors: Viciani
authors: Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy.|University Division of Infectious Diseases, Hospital Department of Specialized and Internal Medicine, Viale Bracci 16, 53100 Siena, Italy.
authors: Francesca
authors: F
authors: Montagnani
authors: GSK Vaccines S.r.l., Via Fiorentina, 1 53100 Siena, Italy.
authors: Simona
authors: S
authors: Tavarini
authors: Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy.
authors: Giacinta
authors: G
authors: Tordini
authors: GSK Vaccines S.r.l., Via Fiorentina, 1 53100 Siena, Italy.
authors: Silvia
authors: S
authors: Maccari
authors: Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy.
authors: Matteo
authors: M
authors: Morandi
authors: GSK Vaccines S.r.l., Via Fiorentina, 1 53100 Siena, Italy.
authors: Elisa
authors: E
authors: Faenzi
authors: Clinica Otorinolaringoiatrica, Policlinico Universitario "Le Scotte", Viale Bracci 16, 53100 Siena, Italy.
authors: Cesare
authors: C
authors: Biagini
authors: Clinica Otorinolaringoiatrica, Policlinico Universitario "Le Scotte", Viale Bracci 16, 53100 Siena, Italy.
authors: Antonio
authors: A
authors: Romano
authors: Clinica Otorinolaringoiatrica, Policlinico Universitario "Le Scotte", Viale Bracci 16, 53100 Siena, Italy.
authors: Lorenzo
authors: L
authors: Salerni
authors: GSK Vaccines S.r.l., Via Fiorentina, 1 53100 Siena, Italy.
authors: Oretta
authors: O
authors: Finco
authors: Section of Pathology, Azienda Ospedaliera Universitaria Senese, Viale Bracci 16, 53100 Siena, Italy.
authors: Stefano
authors: S
authors: Lazzi
authors: GSK Vaccines S.r.l., Via Fiorentina, 1 53100 Siena, Italy.
authors: Paolo
authors: P
authors: Ruggiero
authors: Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100 Siena, Italy.|University Division of Infectious Diseases, Hospital Department of Specialized and Internal Medicine, Viale Bracci 16, 53100 Siena, Italy.
authors: Andrea
authors: A
authors: De Luca
authors: GSK Vaccines S.r.l., Via Fiorentina, 1 53100 Siena, Italy.
authors: Michèle A
authors: MA
authors: Barocchi
authors: GSK Vaccines S.r.l., Via Fiorentina, 1 53100 Siena, Italy.
authors: Andrea G O
authors: AG
authors: Manetti
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000293:Adolescent; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003545:Cysteine / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D016017:Odds Ratio; D014066:Palatine Tonsil / Q000382:microbiology* / Q000473:pathology / Q000601:surgery; D060888:Real-Time Polymerase Chain Reaction; D020181:Sleep Apnea, Obstructive / Q000209:etiology*; D013290:Streptococcal Infections / Q000150:complications* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013301:Streptolysins / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015289:Leukotrienes; D053594:Myeloid Differentiation Factor 88; D013301:Streptolysins; C470409:TICAM1 protein, human; D051197:Toll-Like Receptor 4; C112381:cysteinyl-leukotriene; C025964:streptolysin O; D048051:p38 Mitogen-Activated Protein Kinases; D003545:Cysteine