Torben Sigsgaard1, Hans Jürgen Hoffmann, Peter S Thorne. 1. Department of Environmental and Occupational Medicine, Institute of Public Health, University of Aarhus, Vennelyst Boulevard 6, Aarhus C, Denmark. ts@mil.au.dk
Abstract
PURPOSE OF REVIEW: Discovery of a system of pattern recognition receptors has opened an entirely new field in inflammation research. This paper reviews studies from the last 18 months focusing on mechanisms of immune stimulation after exposure to microbial components and other exposures that induce or modulate innate immune responses. RECENT FINDINGS: Perhaps the most studied pattern recognition receptor response pathway is endotoxin upregulation of cytokine production via lipopolysaccharide binding protein (LBP), soluble and membrane bound CD14, v-myb-dependent gene 2 (MD-2) and toll-like receptor (TLR) 4. This interaction, and that of synthetic TLR2-agonist (Pam3Cys4) with toll-like receptors TLR1 and TLR2, has recently been characterized at the structural level, and has been confirmed by a blunted response in knockout mice. Dectin-1 recognizes the hyphal form, but not the spores of Aspergillus fumigatus, giving the first known function of the dectin receptor. Martinez has hypothesized that inconsistencies relating to the protective effect of lipopolysaccharide exposure on allergy might be explained by a gene-environment interaction. SUMMARY: We are on the brink of understanding the complex nature and interaction of the pattern recognition receptors and the cellular events following their binding of ligands. Further elucidation of gene-environment interactions will probably lead to important discoveries in the near future.
PURPOSE OF REVIEW: Discovery of a system of pattern recognition receptors has opened an entirely new field in inflammation research. This paper reviews studies from the last 18 months focusing on mechanisms of immune stimulation after exposure to microbial components and other exposures that induce or modulate innate immune responses. RECENT FINDINGS: Perhaps the most studied pattern recognition receptor response pathway is endotoxin upregulation of cytokine production via lipopolysaccharide binding protein (LBP), soluble and membrane bound CD14, v-myb-dependent gene 2 (MD-2) and toll-like receptor (TLR) 4. This interaction, and that of synthetic TLR2-agonist (Pam3Cys4) with toll-like receptors TLR1 and TLR2, has recently been characterized at the structural level, and has been confirmed by a blunted response in knockout mice. Dectin-1 recognizes the hyphal form, but not the spores of Aspergillus fumigatus, giving the first known function of the dectin receptor. Martinez has hypothesized that inconsistencies relating to the protective effect of lipopolysaccharide exposure on allergy might be explained by a gene-environment interaction. SUMMARY: We are on the brink of understanding the complex nature and interaction of the pattern recognition receptors and the cellular events following their binding of ligands. Further elucidation of gene-environment interactions will probably lead to important discoveries in the near future.
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