The role of Toll-like receptors and related receptors of the innate immune system in asthma

Abstract

The biology of the innate immunity receptors is of central importance in the host response to the environment. Identifying genetic variants that alter the innate immune response is highly relevant to understanding asthma pathogenesis. This review summarizes recent studies of the role of innate immunity receptors, including Toll-like receptors and CD14, in the pathogenesis of asthma. The majority of studies published since 2004 have been genetic association studies in various clinical settings, which have found positive associations of single nucleotide polymorphisms in TLR2, TLR4, TLR6 and TLR10 with asthma or atopy, although the number of studies is small and the results not yet replicated. The designs for CD14 genetic studies have been more sophisticated and have included gene-environment interaction. The results of CD14 gene associations with asthma and atopy are suggestive but have not been fully replicated. Potential reasons for non-replication of TLR and CD14 association studies include insufficient power, type I error, population heterogeneity and different phenotypes studied. In addition, there may be differences in CD14 genetic effects between childhood and adulthood, and between levels of endotoxin exposure. The evidence is still being accumulated for the role of Toll-like receptor polymorphisms in the pathogenesis of asthma. There is emerging evidence for the role of CD14 polymorphisms in the development of asthma and atopy. Further studies of innate immunity in asthma and allergy are required, using rigorous study design, measurement of environmental exposure and intermediate phenotypes to demonstrate single nucleotide polymorphism functionality.