Open AccessGenetic Variation in Toll-Like Receptor Signalling and the Risk of Inflammatory and Immune Diseases
Author(s) -
Sinéad C. Corr,
Luke A. J. O’Neill
Publication year - 2009
Publication title -
journal of innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.078
H-Index - 64
eISSN - 1662-8128
pISSN - 1662-811X
DOI - 10.1159/000200774
Subject(s) - immunology , immune system , innate immune system , tlr2 , biology , inflammation , pattern recognition receptor , toll like receptor , tlr4 , disease , acquired immune system , medicine , pathology
There has been growing interest in the role of host genetic factors in humans and susceptibility to infectious and inflammatory diseases. Genetic variation in Toll-like receptors (TLRs), key innate immune receptors or their signalling molecules, have been described. Variation in certain TLRs has been linked to disease susceptibility. This genetic variation can result in an altered immune response to pathogenic challenge as well as exorbitant immune activation and inflammation, and thus may influence the pathogenesis or outcome of disease. Examples include variants of TLR4 in sepsis, malaria, inflammatory bowel disease and atherosclerosis; variants in TLR2 in tuberculosis and asthma; a variant in Mal (a key signal for TLR2 and TLR4) in malaria, tuberculosis and systemic lupus erythematosus; and variants in the kinase IRAK4 in pyogenic infections. These associations provide us with a validation for the role of TLRs in human disease, and also suggest possible strategies to limit or boost TLR function in the effort to develop new therapies.