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A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection
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.
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.
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2015 (English)In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 104, 1-9 p., e53084Article in journal (Refereed) PublishedText
Abstract [en]

Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

Place, publisher, year, edition, pages
JOURNAL OF VISUALIZED EXPERIMENTS , 2015. no 104, 1-9 p., e53084
Keyword [en]
Infection; Issue 104; In vitro model; 3D model; 3D analysis; lung tissue; tuberculosis; M. tuberculosis; granuloma
National Category
Cell and Molecular Biology Biomedical Laboratory Science/Technology
URN: urn:nbn:se:liu:diva-125330DOI: 10.3791/53084ISI: 000368572800031PubMedID: 26485646OAI: diva2:905952

Funding Agencies|Swedish Research Council [2012-1951, 2012-3349]; Swedish Foundation for Strategic Research; Karolinska Institutet; Swedish International Development Cooperation Agency (Sida); Swedish Civil Contingencies Agency (MSB); Swedish Heart and Lung Foundation (HLF); Stockholm County Council

Available from: 2016-02-23 Created: 2016-02-19 Last updated: 2016-03-04

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Braian, ClaraLerm, MariaParasa, Venkata R.
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Division of Microbiology and Molecular MedicineFaculty of Medicine and Health Sciences
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