02075nas a2200409   4500000000100000008004100001260001600042653001200058653002800070653001800098653002000116653001900136653001500155653001100170653001500181653001200196653001400208653002500222653003600247653002200283653001100305653002500316100001400341700001100355700001400366700001700380700001200397700001300409700001300422700001600435700001500451245013600466300001100602490000800613520103000621022001401651       2007                            d  c2007 Jun 1510aAlleles10aAmino Acid Substitution10aCell Membrane10aCells, Cultured10aGene Frequency10aHomozygote10aHumans10aIsoleucine10aleprosy10aMonocytes10aMycobacterium leprae10aPolymorphism, Single Nucleotide10aProtein Transport10aSerine10aToll-Like Receptor 11 aJohnson C1 aLyle E1 aOmueti KO1 aStepensky VA1 aYegin O1 aAlpsoy E1 aHamann L1 aSchumann RR1 aTapping RI00aCutting edge: A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy.  a7520-40 v1783 a<p>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.</p>  a0022-1767