Cutting Edge: A Common Polymorphism Impairs Cell Surface Trafficking and Functional Responses of TLR1 but Protects against Leprosy
| Autor: | Richard I. Tapping, Erkan Alpsoy, Elizabeth A. Lyle, Lutz Hamann, Christopher M. Johnson, Ralf R. Schumann, Katherine O. Omueti, Olcay Yegin, Vitaly Stepensky |
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| Rok vydání: | 2007 |
| Předmět: |
Immunology
Cell Heterologous Single-nucleotide polymorphism Polymorphism Single Nucleotide Monocytes Immune system Gene Frequency Leprosy Serine medicine Humans Immunology and Allergy Isoleucine Allele Receptor Mycobacterium leprae Alleles Cells Cultured biology Cell Membrane Homozygote biology.organism_classification Toll-Like Receptor 1 Protein Transport medicine.anatomical_structure Amino Acid Substitution Bacteria |
| Zdroj: | The Journal of Immunology. 178:7520-7524 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | TLRs constitute an essential family of pattern recognition molecules that, through direct recognition of conserved microbial components, initiate inflammatory responses following infection. In this role, TLR1 enables host responses to a variety of bacteria, including pathogenic species of mycobacteria. In this study, we report that I602S, a common single nucleotide polymorphism within TLR1, is associated with aberrant trafficking of the receptor to the cell surface and diminished responses of blood monocytes to bacterial agonists. When expressed in heterologous systems, the TLR1 602S variant, but not the TLR1 602I variant, exhibits the expected deficiencies in trafficking and responsiveness. Among white Europeans, the 602S allele represents the most common single nucleotide polymorphism affecting TLR function identified to date. Surprisingly, the 602S allele is associated with a decreased incidence of leprosy, suggesting that Mycobacterium leprae subverts the TLR system as a mechanism of immune evasion. |
| Databáze: | OpenAIRE |
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