title: Components of Streptococcus pneumoniae suppress allergic airways disease and NKT cells by inducing regulatory T cells.
abstract: Asthma is an allergic airways disease (AAD) caused by dysregulated immune responses and characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). NKT cells have been shown to contribute to AHR in some mouse models. Conversely, regulatory T cells (Tregs) control aberrant immune responses and maintain homeostasis. Recent evidence suggests that Streptococcus pneumoniae induces Tregs that have potential to be harnessed therapeutically for asthma. In this study, mouse models of AAD were used to identify the S. pneumoniae components that have suppressive properties, and the mechanisms underlying suppression were investigated. We tested the suppressive capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply) and CpG. When coadministered, T3P + Ply suppressed the development of: eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR. Importantly, T3P + Ply also attenuated features of AAD when administered during established disease. We show that NKT cells contributed to the development of AAD and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply-induced Tregs were essential for the suppression of NKT cells and AAD, which was demonstrated by Treg depletion. Collectively, our results show that the S. pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that blocked the activity of NKT cells. These data suggest that S. pneumoniae components may have potential as a therapeutic strategy for the suppression of allergic asthma through the induction of Tregs and suppression of NKT cells.
authors.affiliation: Centre for Asthma and Respiratory Disease, Newcastle, New South Wales 2300, Australia.
authors.forename: Alison N
authors.initials: AN
authors.lastname: Thorburn
authors.forename: Paul S
authors.initials: PS
authors.lastname: Foster
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016667:Bacterial Capsules / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000276:immunology / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000737:chemistry* / Q000276:immunology; D013301:Streptolysins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; C413446:type 3 capsular polysaccharide, Streptococcus pneumoniae