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Updated: Jan 30, 2026
23:06
The MODS method for diagnosis of tuberculosis and multidrug resistant tuberculosis
Published on: August 11, 2008
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Spatial Network Mapping of Pulmonary Multidrug-Resistant Tuberculosis Cavities Using RNA Sequencing
Keertan Dheda1,2, Laura Lenders1, Shashikant Srivastava3,4
11Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine and UCT Lung Institute and South African MRC/UCT Centre for the Study of Antimicrobial Resistance, University of Cape Town, Cape Town, South Africa.
American Journal of Respiratory and Critical Care Medicine
|January 30, 2019
Summary
This study maps the complex immune pathways within tuberculosis lung cavities, revealing key inflammatory and signaling differences. Findings highlight potential targets for new host-directed therapies against Mycobacterium tuberculosis.
Area of Science:
- Immunology and Infectious Diseases
- Pathophysiology of Tuberculosis Cavitation
Background:
- Limited understanding of protective immunity and pathogenesis in tuberculosis (TB) cavities.
- Need to elucidate spatially distinct pathophysiological pathways within human TB cavities.
Purpose of the Study:
- To map pathophysiological pathways at anatomically distinct positions within human TB cavities.
- To identify potential targets for host-directed therapies and transmission prevention.
Main Methods:
- Biopsies from 14 multidrug-resistant TB cavities and 10 healthy controls.
- RNA sequencing, immunohistochemistry, and bacterial load determination at 8 cavity locations.
- Spatial mapping of gene expression and computational modeling of immune networks.
Main Results:
- Upregulation of proinflammatory pathways in the cavity wall.
- Downregulation of neuroendocrine, calcium signaling, and immune cell activation pathways at the central caseum-fluid interface.
- Neuroendocrine, PKC-θ, and TREM-1 pathways correlated strongly with bacterial burden, unlike T-helper systems.
Conclusions:
- Novel insights into host immunity and pathogenesis of Mycobacterium tuberculosis-related lung cavitation.
- Defined pathways offer potential targets for host-directed therapies.
- Identified pathways may inform transmission prevention strategies.
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