Commentary Cell Science Reviews Vol 5 No 4 ISSN 1742-8130

Allergens as innate mimics: functional homology to toll-like receptors

A recent landmark study in Nature provides the first evidence that house dust mile allergen Der p 2 can directly facilitate activation of the innate system by specific interaction with Toll-like receptor 4 (TLR4). This ability to facilitate TLR4 activation may confer auto-adjuvant properties that explain the universal propensity of specific allergens, such as Der p 2, to active adaptive T cell responses. This novel work generates a series of new hypotheses that now need to be tested. Here we review these findings and examine the potential implications of this ‘functional mimicry’ in the context of the wider allergy literature. Specifically, we examine the possible role of allergen driven innate immune activation in immune maturation, and how this may vary depending on environmental microbial burden. We also examine these newly recognised properties of Der p 2, and possibly other allergens in initiating and perpetuating local inflammation. The capacity for allergens to activate multiple pathways will clearly also have implications for how we interpret the results of in vitro assays. It is possible that at least some of the previously described in vitro differences in patterns of HDM allergen-responsiveness of allergic and non-allergic individuals could be attributed to differences in Der p 2 facilitated TLR4 signalling. This could reflect previously unrecognised differences in innate immune function that now need to be investigated further.

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