Presymptomatic differences in Toll-like receptor function in infants who have allergy.

Background: Microbial exposure might play a key role in allergy development, but little is known about the role of Tolllike receptors (TLRs). Objective: This study explored the association between neonatal TLR microbial recognition/function, allergy risk (maternal allergy), and prospective allergy development. Methods: Cord blood mononuclear cells (n 5 111) were cultured either alone or with optimal concentrations of TLR ligands: lipoteichoic acid (TLR2), polyinosinicpolycytidylic acid (TLR3), LPS with IFN-g (TLR4), flagellin (TLR5), imiquimod R837 (TLR7), or CpG (TLR9). Cytokine responses were assessed in relation to allergy risk (maternal allergy) and allergy outcomes (sensitization, food allergy, and atopic dermatitis) at 12 months of age. Results: Maternal allergy (n 5 59) was associated with significantly higher neonatal IL-12 and IFN-g responses to TLR2, TLR3, and TLR4 activation, whereas TNF-a and IL-6 responses to TLR2, TLR4, and TLR5 activation were significantly higher in newborns who subsequently had allergic disease (n 5 32). Notably, consistent with previous reports, newborns who had disease had lower TH1 IFN-g response to mitogens (PHA). Conclusion: Allergic disease was associated with increased (rather than decreased) perinatal TLR responses. Further studies are needed to determine how these responses track in the postnatal period and whether this relative hyperresponsiveness is a product of intrauterine influences, including maternal atopy, functional genetic polymorphisms, or both. (J Allergy Clin Immunol 2008;122:391-9.)