The DOI matches its Crossref record; 74 of the 75 references it cites were found in a registry or an index.
The mechanisms and consequences of the extra-pulmonary dissemination of Mycobacterium tuberculosis
Abstract
The dissemination of Mycobacterium tuberculosis from the primary focus of infection is central to the pathogenesis of tuberculosis. Trafficking of bacteria to the regional lymph nodes is essential to the development of a protective T-cell mediated immune response, but bacteria trafficked within the bloodstream can lead to extra-pulmonary dissemination and some of the most devastating clinical consequences of tuberculosis. Yet how M. tuberculosis leaves the lungs is poorly understood. Here, we review the potential pathways and molecular mechanisms behind the dissemination of M. tuberculosis and consider the consequences to both host and bacteria. To disseminate M. tuberculosis must breach the alveolar epithelium and various bacterial factors have been implicated in this process. Heparin binding haemagglutinin adhesin (HBHA) enables M. tuberculosis to bind to sulphated glycoconjugates on epithelial cells; disruption of its synthesis severely impairs the ability of bacteria to disseminate from the lungs to the spleen. Two products of the M. tuberculosis RD1 gene locus, early secretory antigenic target 6 kDa (ESAT-6) and culture filtrate protein 10 kDa (CFP-10), have been linked to cell lysis and may enable bacteria to invade and spread within the alveolar epithelium. Recent studies in embryonic zebrafish indicate ESAT-6 may also stimulate the trafficking of infected macrophages within granulomas, thereby promoting the early dissemination of bacteria. These findings challenge conventional notions of the protective role of granulomas in mycobacterial infection and indicate M. tuberculosis has evolved specific mechanisms which utilise granulomas as foci of macrophage recruitment, infection, and subsequent bacterial dissemination. Further understanding of the pathways, mechanisms and consequences of M. tuberculosis dissemination could have a major impact in designing novel vaccines and therapeutic strategies.
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“Therefore, MTB can multiply and spread to other organs of the body, resulting in extrapulmonary TB.195”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [195]
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Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles
Singh, A. P., Biswas, A., Shukla, A., & Maiti, P. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0068-3 · Cited by 645
Tuberculous meningitis: more questions, still too few answers
Thwaites, G. E., van Toorn, R., & Schoeman, J. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70168-6 · Cited by 482
Self-citationThe immunoregulatory landscape of human tuberculosis granulomas
McCaffrey, E., Donato, M., Keren, L., Chen, Z., Delmastro, A. C., Fitzpatrick, M. B., Gupta, S., Greenwald, N. F., Baranski, A., Graf, W., et al. (2022) · Nature Immunology · doi:10.1038/s41590-021-01121-x · Cited by 334
MAIT Cells in Health and Disease
Provine, N. M., & Klenerman, P. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-080719-015428 · Cited by 232
The pathogenesis of tuberculous meningitis
Davis, A., Rohlwink, U. K., Proust, A. M., Figaji, A. A., & Wilkinson, R. J. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.mr0318-102r · Cited by 201
Metadata
- Authors
- Krishnan, N., Robertson, B. D., & Thwaites, G.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Krishnan, Nitya
- Venue
- Tuberculosis
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 90
- Issue
- 6
- Pages
- 361-366
- ISSN
- 1472-9792 (ISSN-L)
- OpenAlex
- W2059831659
- Cited by
- 178
- References
- 75
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 12 · 2023: 13 · 2022: 20 · 2021: 8 · 2020: 14 · 2019: 12 · 2018: 12 · 2017: 14 · 2016: 15 · 2015: 8 · 2014: 8 · 2013: 7 · 2012: 9
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Tuberculosis (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Health Sciences › Medicine › Infectious Diseases › Diagnosis and treatment of tuberculosis
- Keywords
- Mycobacterium tuberculosis, alveolar epithelium, HBHA, ESAT-6, CFP-10, granuloma, macrophage trafficking, spleen, lymph node trafficking, T cell immunity, zebrafish model
- MeSH terms
- Antigens, Bacterial, Bacterial Proteins, Epithelial Cells, Humans, Lung, Membrane Proteins, Mycobacterium Infections, Mycobacterium tuberculosis, Phagocytes
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