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- Title
Activation and regulation of Toll-like receptors 2 and 1 in human leprosy.
- Authors
Krutzik, Stephan R; Ochoa, Maria Teresa; Sieling, Peter A; Uematsu, Satoshi; Ng, Yolanda W; Legaspi, Annaliza; Liu, Philip T; Cole, Stewart T; Godowski, Paul J; Maeda, Yumi; Sarno, Euzenir N; Norgard, Michael V; Brennan, Patrick J; Akira, Shizuo; Rea, Thomas H; Modlin, Robert L
- Abstract
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.
- Publication
Nature medicine, 2003, Vol 9, Issue 5, p525
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/nm864