title: TLR ligands of ryegrass pollen microbial contaminants enhance Th1 and Th2 responses and decrease induction of Foxp3(hi) regulatory T cells.
abstract: Microbial contamination of grass pollens could affect sensitization, subsequent allergic response, and efficacy of allergen-specific immunotherapy. We investigated whether bacterial immunomodulatory substances can direct PBMC responses of allergic and nonatopic subjects against ryegrass pollen (RGP) toward Th1, Th2, or regulatory T (Treg) cells. Aqueous extracts of RGP with high or low LPS were fractionated into large and small molecular weight (MW) components by diafiltration. CFSE-labeled PBMCs from allergic and nonatopic subjects were stimulated with RGP extracts (RGPEs) and analyzed for cytokine secretion and T-cell responses. High LPS RGPE increased IFN-γ(+) Th1 and IL-4(+) Th2 effector cell induction and consistently decreased CD4(+) Foxp3(hi) Treg-cell induction. IL-10-producing T-cell frequency was unaltered, but IL-10 secretion was increased by high LPS RGPE. RGPE-stimulation of TLR-transfected cell lines revealed that high LPS pollen also contained a TLR2-ligand, and both batches a TLR9-ligand. Beta-1,3-glucans were detected in large and small MW fractions and were also T-cell stimulatory. In conclusion, coexposure to allergen and proinflammatory microbial stimuli does not convert an established Th2- into a Th1-response. Instead, proinflammatory responses are exacerbated and Foxp3(hi) Treg-cell induction is decreased. These findings show that adjuvants for specific immunotherapy should enhance Treg cells rather than target immune deviation from Th2 to Th1.
authors.affiliation: Department of Immunology, Monash University, Melbourne, Australia. dianamittag@gmail.com
authors.forename: Diana
authors.initials: D
authors.lastname: Mittag
authors.forename: Nirupama
authors.initials: N
authors.lastname: Varese
authors.forename: Anja
authors.initials: A
authors.lastname: Scholzen
authors.forename: Ashley
authors.initials: A
authors.lastname: Mansell
authors.forename: Gillian
authors.initials: G
authors.lastname: Barker
authors.forename: Gregory
authors.initials: G
authors.lastname: Rice
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Rolland
authors.forename: Robyn E
authors.initials: RE
authors.lastname: O'Hehir
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008129:Lolium / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D010936:Plant Extracts / Q000737:chemistry / Q000276:immunology; D011058:Pollen / Q000276:immunology* / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000485:Allergens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018836:Inflammation Mediators; D008024:Ligands; D008070:Lipopolysaccharides; D010936:Plant Extracts; D051193:Toll-Like Receptors; D016753:Interleukin-10