Cutting edge: A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy


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Johnson C. M., Lyle E. A., Omueti K. O., Stepensky V. A., Yegin C., Alpsoy E., ...More

JOURNAL OF IMMUNOLOGY, vol.178, no.12, pp.7520-7524, 2007 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 178 Issue: 12
  • Publication Date: 2007
  • Doi Number: 10.4049/jimmunol.178.12.7520
  • Journal Name: JOURNAL OF IMMUNOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.7520-7524
  • Akdeniz University Affiliated: Yes

Abstract

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 6021 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.