The Role of the Granuloma in Expansion and Dissemination of Early Tuberculous Infection

By J. Davis, L. Ramakrishnan. Cell, 2009

900 citations recorded by the source corpus.

SUMMARY Granulomas, organized aggregates of immune cells, form in response to persistent stimuli and are hallmarks of tuberculosis. Tuberculous granulomas have long been considered host-protective structures formed to contain infection. However, work in zebrafish infected with Mycobacterium marinum suggests that granulomas contribute to early bacterial growth. Here we use quantitative intravital microscopy to reveal distinct steps of granuloma formation and assess their consequence for infection. Intracellular mycobacteria use theESX-1/RD1virulence locus to induce recruitment of new macrophages to, and their rapid movement within, nascent granulomas. This motility enables multiple arriving macrophages to efficiently find and phagocytose infected macrophages undergoing apoptosis, leading to rapid, iterative expansion of infected macrophages and thereby bacterial numbers. The primary granuloma then seeds secondary granulomas via egress of infected macrophages. Our direct observations provide insight into how pathogenic mycobacteria exploit the granuloma during the innate immune phase for local expansion and systemic dissemination.

Subfields: Epidemiology, Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/dfd4b5c6155503c24b3c5a6e6b3c452a12ff58d3

How researchers see this paper

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In Epidemiology

1. A. O’Garra
2. R. Wilkinson
3. D. Russell
4. M. Berry
5. Finlay W Mcnab
6. Paul S. Redford
7. C. Bloom

In Immunology

1. A. O’Garra
2. D. Russell

In Infectious Diseases

1. A. O’Garra
2. R. Wilkinson
3. D. Russell
4. M. Berry
5. Finlay W Mcnab
6. Paul S. Redford
7. C. Bloom

Citations in the corpus

• Foamy macrophages and the progression of the human TB granuloma (2009, background): “The direct influence of the bacterium is clear even in 'pared-down' models, such as the zebrafish, that rely solely on the innate immune response at the early stage of developmen”
• The immune response in tuberculosis. (2013, methodology): “This suggests that the mycobacteria are using the host to facilitate the spread of infection (109, 110).”