Allergy 2013 May (2)-8

TLR ligands of ryegrass pollen microbial contaminants enhance Th1 and Th2 responses and decrease induction of Foxp3(hi) regulatory T cells.

Eur J Immunol. 2013 Mar;43(3):723-33

Mittag D, Varese N, Scholzen A, Mansell A, Barker G, Rice G, Rolland JM, O’Hehir RE.

Department of Immunology, Monash University, Melbourne, Australia. dianamittag@gmail.com

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. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PMID: 23238878

 

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Dr Diana Mittag

To Bug or Not To Bug – treatment with ‘dirty’ pollen extract may reinforce an established allergic response

Specific allergen-immunotherapy, the only curative treatment for allergy, involves repeated doses of allergen extracts to achieve de-sensitisation and tolerance. Varying levels of microbial extract contamination may modulate immune-responses – but whether such contamination is beneficial or detrimental to clinical efficacy has not been clarified to date.

Mittag et al. demonstrate that ryegrass pollen-associated PAMPs, such as LPS, enhance the pre-established Th2-bias in peripheral blood samples from allergic subjects. This resulted from increased inflammatory cytokine secretion, including Th2-cytokines, and increased Th2 cell induction with impaired Foxp3hi Treg induction. Only minor differences were observed in IL-10 secreting T cell induction with negligible IL-17 secretion. This was similar in non-atopic subjects but with a reduction in the Th2 response.

These data provide important insight into adjuvant properties of pollen microbial contaminants and suggest that adjuvants for allergen-specific immunotherapy should enhance Treg cells rather than target immune deviation from Th2 to Th1.

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