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Modeling Mycobacterium tuberculosis early granuloma formation in experimental human lung tissue
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Karolinska Institute, Sweden.
Karolinska Institute, Sweden .
Karolinska Institute, Sweden .
Karolinska Institute, Sweden .
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2014 (English)In: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 7, no 2, 281-288 p.Article in journal (Refereed) Published
Abstract [en]

The widely used animal models for tuberculosis ( TB) display fundamental differences from human TB. Therefore, a validated model that recapitulates human lung TB is attractive for TB research. Here, we describe a unique method for establishment of TB infection in an experimental human lung tissue model. The model is based on cell lines derived from human lungs and primary macrophages from peripheral blood, and displays characteristics of human lung tissue, including evenly integrated macrophages throughout the epithelium, production of extracellular matrix, stratified epithelia and mucus secretion. Establishment of experimental infection in the model tissue with Mycobacterium tuberculosis, the bacterium that causes TB, resulted in clustering of macrophages at the site of infection, reminiscent of early TB granuloma formation. We quantitated the extent of granuloma formation induced by different strains of mycobacteria and validated our model against findings in other TB models. We found that early granuloma formation is dependent on ESAT-6, which is secreted via the type VII secretion machinery of virulent mycobacteria. Our model, which can facilitate the discovery of the interactions between mycobacteria and host cells in a physiological environment, is the first lung tissue model described for TB.

Place, publisher, year, edition, pages
Company of Biologists: OAJ / Company of Biologists , 2014. Vol. 7, no 2, 281-288 p.
Keyword [en]
Tuberculosis; M. tuberculosis; Granuloma; In vitro model; Lung tissue; ESX-1
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-108941DOI: 10.1242/dmm.013854ISI: 000337619300015OAI: oai:DiVA.org:liu-108941DiVA: diva2:734185
Available from: 2014-07-15 Created: 2014-07-13 Last updated: 2017-12-05

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Lerm, Maria

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