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

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-gamma responses, the purified TLR2 ligands lipoteichoic acid and Pam3CSK4 inhibited HDM-specific IFN-gamma 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 T(H)2 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 T(H)1 immune response.

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