Recognition of Streptococcus pneumoniae and MDP by NOD2 results in a potent induction of MMP-9, which can be controlled by LPS stimulation.

Infect Immun. 2014 Sep 2. pii: IAI.02150-14. [Epub ahead of print]

Recognition of Streptococcus pneumoniae and MDP by NOD2 results in a potent induction of MMP-9, which can be controlled by LPS stimulation.

Vissers M1, Hartman Y1, Groh L1, de Jong DJ2, de Jonge MI1, Ferwerda G3.

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Abstract

Matrix metallopeptidase-9 (MMP-9) is a protease involved in the degradation of extracellular matrix collagen. Evidence suggests that MMP-9 is involved in the pathogenesis during a Streptococcus pneumoniae infection. However, not much is known about the induction of MMP-9 and the regulatory processes involved. We show that the Gram-positive bacteria used in this study induce high amounts of MMP-9 in contrast to the Gram-negative bacteria that were used. An important PAMP for Gram-positive bacteria is muramyl dipeptide (MDP). MDP is a very potent inducer of MMP-9 and showed a dose-dependent MMP-9 induction. Experiments using PBMCs from Crohn's disease patients with a non-functional NOD2 show that MMP-9 induction by Streptococcus pneumoniae and MDP is NOD2 dependent. Increasing amounts of LPS, an important PAMP for Gram-negative bacteria, resulted in decreasing amounts of MMP-9. Moreover, the induction of MMP-9 by MDP could be counteracted by simultaneously adding LPS. The inhibition of MMP-9 expression by LPS was found to be post-transcriptional regulated, independent of metalloproteinase-1 (TIMP-1), an endogenous inhibitor of MMP-9. Collectively, these data show that Streptococcus pneumoniae is able to induce high amounts of MMP-9. These high MMP-9 levels could potentially be involved in Streptococcus pneumoniae pathogenesis.

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PMID: 25183734 [PubMed - as supplied by publisher]