title: Bacterial capsular polysaccharide prevents the onset of asthma through T-cell activation.
abstract: Over the last four decades, increases in the incidence of immune-mediated diseases in the Western world have been linked to changes in microbial exposure. It is becoming increasingly clear that the normal microbiota in the gut can profoundly alter susceptibility to a wide range of diseases, such as asthma, in which immune homeostasis is disrupted, yet the mechanisms governing this microbial influence remains poorly defined. In this study, we show that gastrointestinal exposure to PSA, a capsular polysaccharide derived from the commensal bacterium Bacteroides fragilis, significantly limits susceptibility to the induction of experimental asthma. We report that direct treatment of mice with PSA generates protection from asthma, and this effect can be given to a naïve recipient by adoptive transfer of CD4(+) T cells from PSA-exposed mice. Remarkably, we found that these PSA-induced T cells are not canonical FoxP3(+) regulatory T cells, but that they potently inhibit both Th1 and Th2 models of asthma in an IL-10-dependent fashion. These findings reveal that bacterial polysaccharides link the microbiota with the peripheral immune system by activating CD4(+)Foxp3(-) T cells upon exposure in the gut, and they facilitate resistance to unnecessary inflammatory responses via the production of IL-10.
authors.affiliation: Department of Pathology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Johnson
authors.affiliation: Department of Pathology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Jones
authors.affiliation: Department of Pathology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA brian.cobb@case.edu bac28@case.edu.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Cobb
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D016753:Interleukin-10 / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D018927:Anti-Asthmatic Agents; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011135:Polysaccharides, Bacterial; D016753:Interleukin-10
keywords: Bacteroides fragilis; PSA; asthma; hygiene hypothesis