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TLR ligands of ryegrass pollen microbial contaminants enhance Th1 and Th2 responses and decrease induction of Foxp3(hi) regulatory T cells.
Mittag, Diana; Varese, Nirupama; Scholzen, Anja; Mansell, Ashley; Barker, Gillian; Rice, Gregory; Rolland, Jennifer M; O'Hehir, Robyn E.
Afiliação
  • Mittag D; Department of Immunology, Monash University, Melbourne, Australia. dianamittag@gmail.com
Eur J Immunol ; 43(3): 723-33, 2013 Mar.
Article em En | MEDLINE | ID: mdl-23238878
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pólen / Lolium / Alérgenos / Linfócitos T Reguladores / Células Th2 / Células Th1 / Receptores Toll-Like Limite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Immunol Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Austrália

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pólen / Lolium / Alérgenos / Linfócitos T Reguladores / Células Th2 / Células Th1 / Receptores Toll-Like Limite: Adult / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Immunol Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Austrália