000151245 001__ 151245
000151245 005__ 20181203021958.0
000151245 022__ $$a1078-8956
000151245 02470 $$2PMID$$a12692544
000151245 0247_ $$2doi$$a10.1038/nm864
000151245 037__ $$aARTICLE
000151245 245__ $$aActivation and regulation of Toll-like receptors 2 and 1 in human leprosy
000151245 269__ $$a2003
000151245 260__ $$c2003
000151245 336__ $$aJournal Articles
000151245 520__ $$aThe expression and activation of Toll-like receptors (TLRs) was investigated in leprosy, a spectral disease in which clinical manifestations correlate with the type of immune response mounted toward Mycobacterium leprae. TLR2-TLR1 heterodimers mediated cell activation by killed M. leprae, indicating the presence of triacylated lipoproteins. A genome-wide scan of M. leprae detected 31 putative lipoproteins. Synthetic lipopeptides representing the 19-kD and 33-kD lipoproteins activated both monocytes and dendritic cells. Activation was enhanced by type-1 cytokines and inhibited by type-2 cytokines. In addition, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced TLR1 expression in monocytes and dendritic cells, respectively, whereas IL-4 downregulated TLR2 expression. TLR2 and TLR1 were more strongly expressed in lesions from the localized tuberculoid form (T-lep) as compared with the disseminated lepromatous form (L-lep) of the disease. These data provide evidence that regulated expression and activation of TLRs at the site of disease contribute to the host defense against microbial pathogens.
000151245 700__ $$aKrutzik, Stephan R
000151245 700__ $$aOchoa, Maria Teresa
000151245 700__ $$aSieling, Peter A
000151245 700__ $$aUematsu, Satoshi
000151245 700__ $$aNg, Yolanda W
000151245 700__ $$aLegaspi, Annaliza
000151245 700__ $$aLiu, Philip T
000151245 700__ $$0243892$$g177247$$aCole, Stewart T
000151245 700__ $$aGodowski, Paul J
000151245 700__ $$aMaeda, Yumi
000151245 700__ $$aSarno, Euzenir N
000151245 700__ $$aNorgard, Michael V
000151245 700__ $$aBrennan, Patrick J
000151245 700__ $$aAkira, Shizuo
000151245 700__ $$aRea, Thomas H
000151245 700__ $$aModlin, Robert L
000151245 773__ $$j9$$tNature medicine$$k5$$q525-32
000151245 909C0 $$xU11742$$0252302$$pUPCOL
000151245 909CO $$pSV$$particle$$ooai:infoscience.tind.io:151245
000151245 937__ $$aEPFL-ARTICLE-151245
000151245 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000151245 980__ $$aARTICLE