Activation and regulation of Toll-like receptors 2 and 1 in human leprosy

SR Krutzik, MT Ochoa, PA Sieling, S Uematsu… - Nature medicine, 2003 - nature.com
SR Krutzik, MT Ochoa, PA Sieling, S Uematsu, YW Ng, A Legaspi, PT Liu, ST Cole
Nature medicine, 2003nature.com
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 …
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)-γ 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.
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