@article{3178,
  keywords = {Animals, Cytokines, Humans, Immunity, Innate, leprosy, Lipoproteins, Membrane Glycoproteins, Mice, Receptors, Cell Surface, Toll-Like Receptor 1, Toll-Like Receptor 2, Toll-Like Receptors},
  author = {Krutzik SR and Ochoa MT and Sieling PA and Uematsu S and Ng Y and Legaspi A and Liu PT and Cole S and Godowski PJ and Maeda Y and Sarno E and Norgard MV and Brennan PJ and Akira S and Rea T and Modlin RL},
  title = {Activation and regulation of Toll-like receptors 2 and 1 in human leprosy.},
  abstract = {<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>},
  year = {2003},
  journal = {Nature medicine},
  volume = {9},
  pages = {525-32},
  month = {2003 May},
  issn = {1078-8956},
  doi = {10.1038/nm864},
  language = {eng},
}