Guilt by intimate association: what makes an allergen an allergen?

Why specific, ubiquitous, otherwise innocuous environmental proteins tend to provoke maladaptive, T(H)2-polarized immune responses in susceptible hosts is a fundamental mechanistic question for those interested in the pathogenesis, therapy, and prevention of allergic disease. The current renaissance in the study of innate immunity has provided important insights into this question. The theme emerging from recent studies is that direct (dys)functional interactions with pathways of innate immune activation that evolved to signal the presence of microbial infection are central to the molecular basis for allergenicity. This article reviews these data.