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

Christopher M. Johnson, Elizabeth A. Lyle, Katherine O. Omueti, Vitaly A. Stepensky, Olcay Yegin, Erkan Alpsoy, Lutz Hamann, Ralf R. Schumann, Richard I. Tapping

Research output: Contribution to journalArticle

196 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)7520-7524
Number of pages5
JournalJournal of Immunology
Volume178
Issue number12
StatePublished - Jun 15 2007

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Leprosy
Single Nucleotide Polymorphism
Alleles
Immune Evasion
Mycobacterium leprae
Cell Surface Receptors
Mycobacterium
Monocytes
Bacteria
Incidence
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Johnson, C. M., Lyle, E. A., Omueti, K. O., Stepensky, V. A., Yegin, O., Alpsoy, E., ... Tapping, R. I. (2007). Cutting edge: A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. Journal of Immunology, 178(12), 7520-7524.

Cutting edge : A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. / Johnson, Christopher M.; Lyle, Elizabeth A.; Omueti, Katherine O.; Stepensky, Vitaly A.; Yegin, Olcay; Alpsoy, Erkan; Hamann, Lutz; Schumann, Ralf R.; Tapping, Richard I.

In: Journal of Immunology, Vol. 178, No. 12, 15.06.2007, p. 7520-7524.

Research output: Contribution to journalArticle

Johnson, CM, Lyle, EA, Omueti, KO, Stepensky, VA, Yegin, O, Alpsoy, E, Hamann, L, Schumann, RR & Tapping, RI 2007, 'Cutting edge: A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy', Journal of Immunology, vol. 178, no. 12, pp. 7520-7524.
Johnson, Christopher M. ; Lyle, Elizabeth A. ; Omueti, Katherine O. ; Stepensky, Vitaly A. ; Yegin, Olcay ; Alpsoy, Erkan ; Hamann, Lutz ; Schumann, Ralf R. ; Tapping, Richard I. / Cutting edge : A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. In: Journal of Immunology. 2007 ; Vol. 178, No. 12. pp. 7520-7524.
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