Allergy Takes its Toll: The Role of Toll-like Receptors in Allergy Pathogenesis

Reduced early microbial exposure in early life has become a leading candidate to explain the escalating rate of allergic disease and has generated intense interest in the interaction between the developing immune system and the microbial environment. Infants depend on "signal" from the microbial environment to mature both T-helper cell type 1 and regulatory immune function. These signals, mediated through microbial pattern-recognition receptors, namely toll-like receptors (TLRs), seem essential to achieving the immunologic balance required for (1) pathogen protection and (2) normal immune tolerance. Despite this, the normal development of TLR function has never been documented. There is preliminary evidence that TLR function is under the influence of both genetic factors (genetic polymorphisms) and early environmental exposures including microbial exposure and breast feeding, and maternal smoking. This review explores the evidence that allergy is associated with developmental variations in TLR-mediated immune function and how this may be relevant for disease prevention.