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Mycobacterium tuberculosis growth at the cavity surface: a microenvironment with failed immunity
Gilla Kaplan1, Frank A Post, Andre L Moreira
1Laboratory of Mycobacterial Immunity and Pathogenesis, Newark, New Jersey, USA. kaplan@phri.org
Infection and Immunity
|November 26, 2003
Summary
Immune cells fail to control tuberculosis (TB) in some patients because T cells are absent from lung cavity surfaces, allowing Mycobacterium tuberculosis to grow. This localized immune cell absence, not general immune suppression, explains TB treatment failure.
Area of Science:
- Immunology
- Microbiology
- Pulmonology
Background:
- Pulmonary tuberculosis (TB) control relies on lung granulomas with T cells and macrophages producing cytokines.
- In most immunocompetent individuals, this immune response successfully contains Mycobacterium tuberculosis infection.
Purpose of the Study:
- Investigate the reasons for immune failure in the 10% of individuals with incurable TB.
- Analyze lung lesions from patients undergoing surgery for advanced TB to understand immune evasion mechanisms.
Main Methods:
- Histologic examination of lung lesions from six TB patients.
- Analysis of Mycobacterium tuberculosis mutation profiles and drug resistance.
- Cytokine gene expression analysis.
- Assessment of CD4(+) and CD8(+) T cell distribution within granulomas.
Main Results:
- Heterogeneous distribution of bacilli, with high numbers found in airway-connected cavities.
- Acquisition of drug resistance by Mycobacterium tuberculosis, particularly at cavity surfaces.
- Up-regulated cytokine mRNA in all lesions, indicating no generalized immune suppression.
- Selective absence of T cells (CD4(+) and CD8(+)) at the luminal surface of cavities, hindering T cell-macrophage interaction.
Conclusions:
- Failure to control TB is linked to the localized absence of T cells in lung cavities, creating a permissive environment for bacillary growth.
- Efficient bacterial control occurs in granuloma microenvironments where T cells and macrophages colocalize.
- Understanding these spatial immune dynamics is crucial for developing effective TB therapies.