Journal article
The Role of the Granuloma in Expansion and Dissemination of Early Tuberculous Infection
Cell, Vol.136(1), pp.37-49
2009
DOI: 10.1016/j.cell.2008.11.014
PMCID: PMC3134310
PMID: 19135887
Abstract
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 the ESX-1/RD1 virulence 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.
Details
- Title: Subtitle
- The Role of the Granuloma in Expansion and Dissemination of Early Tuberculous Infection
- Creators
- J. Muse Davis - Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, GA 30322, USALalita Ramakrishnan - Departments of Microbiology, Medicine, and Immunology, University of Washington, Seattle, WA 98195, USA
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.136(1), pp.37-49
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cell.2008.11.014
- PMID
- 19135887
- PMCID
- PMC3134310
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Language
- English
- Date published
- 2009
- Academic Unit
- Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984093225802771
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