02219nas a2200457   4500000000100000008004100001260001300042653001200055653001400067653001100081653002100092653001200113653001700125653002700142653000900169653002800178653002500206653002500231653002400256100001500280700001300295700001500308700001400323700000900337700001400346700001100360700001100371700001600382700001200398700001200410700001500422700001500437700001200452700001000464700001400474245007900488300001100567490000600578520116300584022001401747       2003                            d  c2003 May10aAnimals10aCytokines10aHumans10aImmunity, Innate10aleprosy10aLipoproteins10aMembrane Glycoproteins10aMice10aReceptors, Cell Surface10aToll-Like Receptor 110aToll-Like Receptor 210aToll-Like Receptors1 aKrutzik SR1 aOchoa MT1 aSieling PA1 aUematsu S1 aNg Y1 aLegaspi A1 aLiu PT1 aCole S1 aGodowski PJ1 aMaeda Y1 aSarno E1 aNorgard MV1 aBrennan PJ1 aAkira S1 aRea T1 aModlin RL00aActivation and regulation of Toll-like receptors 2 and 1 in human leprosy.  a525-320 v93 a<p>The expression and activation of Toll-like receptors (TLRs) was investigated in leprosy, a spectral disease in which clinical manifestations correlate with the type of immune response mounted toward Mycobacterium leprae. TLR2-TLR1 heterodimers mediated cell activation by killed M. leprae, indicating the presence of triacylated lipoproteins. A genome-wide scan of M. leprae detected 31 putative lipoproteins. Synthetic lipopeptides representing the 19-kD and 33-kD lipoproteins activated both monocytes and dendritic cells. Activation was enhanced by type-1 cytokines and inhibited by type-2 cytokines. In addition, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced TLR1 expression in monocytes and dendritic cells, respectively, whereas IL-4 downregulated TLR2 expression. TLR2 and TLR1 were more strongly expressed in lesions from the localized tuberculoid form (T-lep) as compared with the disseminated lepromatous form (L-lep) of the disease. These data provide evidence that regulated expression and activation of TLRs at the site of disease contribute to the host defense against microbial pathogens.</p>  a1078-8956