Toll-like receptor 2 is important for the T_H1 response to cutaneous sensitization

Background

Atopic dermatitis and allergic contact dermatitis are skin disorders triggered by epicutaneous sensitization with protein antigens and contact sensitization with haptens, respectively. Skin is colonized with bacteria, which are a source of Toll-like receptor (TLR) 2 ligands.

Objective

We sought to examine the role of TLR2 in murine models of atopic dermatitis and allergic contact dermatitis.

Methods

TLR2^−/− mice and wild-type littermates were epicutaneously sensitized with ovalbumin (OVA) or contact sensitized with oxazolone (OX). Skin histology was assessed by means of hematoxylin and eosin staining and immunohistochemistry. Ear swelling was measured with a micrometer. Cytokine mRNA expression was examined by means of quantitative RT-PCR. Antibody levels and splenocyte secretion of cytokines in response to OVA stimulation were measured by means of ELISA. Dendritic cells were examined for their ability to polarize T-cell receptor/OVA transgenic naive T cells to T_H1 and T_H2.

Results

In response to OVA sensitization, TLR2^−/− mice experienced skin infiltration with eosinophils and CD4⁺ cells, as well as upregulation of T_H2 cytokine mRNAs that was comparable with that seen in wild-type littermates. In contrast, epidermal thickening, IFN-γ expression in the skin, IFN-γ production by splenocytes, and IgG2a anti-OVA antibody levels were impaired in TLR2^−/− mice. After OX ear challenge, contact sensitized TLR2^−/− mice exhibited defective ear swelling with impaired cellular infiltration, decreased epidermal thickening and local IFN-γ expression, and impaired OX-specific IgG2a responses. Dendritic cells from TLR2^−/− mice induced significantly lower production of IFN-γ but normal IL-4 and IL-13 production in naive T cells.

Conclusions

These results indicate that TLR2 promotes the IFN-γ response to cutaneously introduced antigens.

Key words: Toll-like receptor 2, atopic dermatitis, contact hypersensitivity, oxazolone

Abbreviations used: ACD, Allergic contact dermatitis, AD, Atopic dermatitis, AHR, Airway hyperresponsiveness, DC, Dendritic cell, NF-κB, Nuclear factor κB, OVA, Ovalbumin, OX, Oxazolone, TLR, Toll-like receptor, WT, Wild-type