A variety of Mycobacterium tuberculosis cell wall components induce expression of matrix metalloproteinase 9 (MMP-9) by monocytic cells and levels of MMP-9 in vivo positively correlate with severity of disease. Toll-like receptor (TLR)2 mediates cellular responses to acylated molecules but can also mediate responsiveness to diverse molecular structures, including non-acylated native viral and bacterial proteins. MPT/B-83 is a cell-associated lipoglycoprotein common to M tuberculosis and M bovis and an important antigen during infection of cattle Since MPB83 is acylated and glycosylated, we investigated whether MPB83 would induce MMP-9 expression via interaction with TLR2, and assessed the contribution of the lipid, glycan and polypeptide components to its activity. Acylated peptide derived from MPB83 stimulated MMP-9 expression by human macrophage cells via interaction with both TLR2 and TLR1. but not TLR4 Lesser induction was found with secreted (non-acylated, but glycosylated) MPB83 protein purified from culture of M bovis Stimulation of cells with MPB83 induced TNF-alpha production which acted to upregulate MMP-9 expression Surprisingly, recombinant MPB83 protein devoid of any post-translational modification also induced MMP-9 expression. Direct interaction of RecMPB83 with TLR2 was demonstrated by surface plasmon-resonance MPB83 may act as a virulence factor through TLR2 mediated induction of MMP-9 Crown Copyright (C) 2010 Published by Elsevier Inc All rights reserved