Of T Cells and Tolls

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Science  25 Apr 2003:
Vol. 300, Issue 5619, pp. 553
DOI: 10.1126/science.300.5619.553c

Leprosy occurs as distinct clinical phenotypes, with more resistant patients presenting localized skin lesions and susceptible individuals afflicted with a systemically disseminated form of the disease. Clear differences in the magnitude and type of immune response correlate with these two forms, suggesting a direct immunological influence on how the disease advances.

Krutzik et al. show that Toll-like receptors (TLRs) of the innate immune system are differentially activated in response to the leprosy bacillus, Mycobacterium leprae. Cellular activation by killed M. leprae required TLR2 but could be intensified by coexpression of TLR1, suggesting dual contributions from TLR2 homodimers and TLR1-TLR2 heterodimers. Two potential lipoprotein ligands for these TLRs, identified from a genome-wide scan of M. leprae, also elicited a response. Activation by a synthetic form of one of these ligands and TLR1-TLR2 expression were both enhanced by T helper cell type 1 (TH1)-associated cytokine, but diminished by TH2 cytokines. Increased TLR expression in leprosy skin lesions from resistant patients, who are known to express elevated levels of TH1 cytokines, was also apparent. Thus, the modulation of TLR expression and activation by cytokines may determine immunological status and clinical outcome in this disease.—SJS

Nature Med. 10.1038/nm864 (2003).

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