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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MTB can multiply and spread to other organs, resulting in extrapulmonary TB.
“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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- 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 › Surgery › Infectious Diseases and Tuberculosis
- Health Sciences › Medicine › Surgery › 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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