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Inhibition of Tissue Matrix Metalloproteinases Interferes with Mycobacterium tuberculosis-Induced Granuloma Formation and Reduces Bacterial Load in a Human Lung Tissue Model
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Karolinska Institute, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
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2017 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 8, article id 2370Article in journal (Refereed) Published
Abstract [en]

Granulomas are hallmarks of pulmonary tuberculosis (TB) and traditionally viewed as host-protective structures. However, recent evidence suggest that Mycobacterium tuberculosis (Mtb) uses its virulence factors to stimulate the formation of granuloma. In the present study, we investigated the contribution of matrix metalloproteinases (MMPs), host enzymes that cause degradation of the extracellular matrix, to granuloma formation and bacterial load in Mtb-infected tissue. To this end, we used our lung tissue model for TB, which is based on human lung-derived cells and primary human monocyte-derived macrophages. Global inhibition of MMPs in the Mtb-infected tissue model reduced both granuloma formation and bacterial load. The infection caused upregulation of a set of MMPs (MMP1, 3, 9, and 12), and this finding could be validated in lung biopsies from patients with non-cavitary TB. Data from this study indicate that MMP activation contributes to early TB granuloma formation, suggesting that host-directed, MMP-targeted intervention could be considered as adjunct therapy to TB treatment.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2017. Vol. 8, article id 2370
Keywords [en]
matrix metalloproteinases; tuberculosis; tissue inhibitor of matrix metalloproteinases; tissue models; granuloma
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-143911DOI: 10.3389/fmicb.2017.02370ISI: 000417045100001PubMedID: 29259583OAI: oai:DiVA.org:liu-143911DiVA, id: diva2:1170032
Note

Funding Agencies|Swedish Research Council [2014-02289, 2015-02593]; Swedish Heart. Lung Foundation [20130685, 20150709]

Available from: 2018-01-02 Created: 2018-01-02 Last updated: 2018-01-26

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