Toll-like receptor 2 ligands inhibit TH2 responses to mite allergen

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Abstract

Background

There is intense interest in the interaction between microbial compounds and allergy. Although Toll-like receptor (TLR)–2 ligands derived from Gram-positive bacteria alter allergic sensitization in animal models, it is not clear what effect TLR2 ligands have on allergen-specific T-cell memory in human beings.

Objective

To determine whether in vitro exposure to TLR2 ligands modifies the immune response to house dust mite allergen (HDM).

Methods

Blood mononuclear cells were obtained from individuals both allergic (n = 23) and not allergic (n = 22) to HDM, and stimulated with HDM in the presence or absence of TLR2 ligands.

Results

In subjects allergic to HDM, IL-5 and IL-13 responses to HDM were inhibited by heat-killed Staphylococcus aureus, staphylococcal lipoteichoic acid, and the synthetic lipoprotein Pam3CSK4 (P < .005; all stimuli). Although the whole staphylococcal bacteria increased IFN-γ responses, the purified TLR2 ligands lipoteichoic acid and Pam3CSK4 inhibited HDM-specific IFN-γ synthesis. In contrast, TLR2 ligands had minimal effects on responses to HDM in subjects without allergy. TLR2 ligands induced upregulation of HLA-DR expression but did not inhibit antigen uptake or processing by antigen-presenting cells.

Conclusion

Toll-like receptor 2 ligands inhibit allergen-specific TH2 responses in sensitized individuals. This effect appears to be mediated by the actions of TLR2 ligands on antigen-presenting cells, and at least for the purified TLR2 ligands does not involve the induction of a strong TH1 immune response.

Clinical implications

These findings provide an impetus for further preclinical studies examining the potential use of TLR2 ligands in allergic disease.

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