Journal article
Tuberculous Granuloma Induction via Interaction of a Bacterial Secreted Protein with Host Epithelium
Science (American Association for the Advancement of Science), Vol.327(5964), pp.466-469
01/22/2010
DOI: 10.1126/science.1179663
PMCID: PMC3125975
PMID: 20007864
Abstract
Granulomas, organized aggregates of immune cells, are a hallmark of tuberculosis, and have traditionally been thought to restrict mycobacterial growth. However, analysis of
Mycobacterium marinum
in zebrafish has shown that the early granuloma facilitates mycobacterial growth; uninfected macrophages are recruited to the granuloma where they are productively infected by
M. marinum
. Here, we identified the molecular mechanism by which mycobacteria induce granulomas: the bacterial secreted protein ESAT-6, which has long been implicated in virulence, induced matrix metalloproteinase-9 (MMP9) in epithelial cells neighboring infected macrophages. MMP9 enhanced recruitment of macrophages, which contributed to nascent granuloma maturation and bacterial growth. Disruption of MMP9 function attenuated granuloma formation and bacterial growth. Thus, interception of epithelial MMP9 production could hold promise as a host-targeting tuberculosis therapy.
Details
- Title: Subtitle
- Tuberculous Granuloma Induction via Interaction of a Bacterial Secreted Protein with Host Epithelium
- Creators
- Hannah E Volkman - Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA, USATamara C Pozos - Department of Pediatrics, University of Washington, Seattle, WA, USAJohn Zheng - Department of Pediatrics, University of Washington, Seattle, WA, USAJ. Muse Davis - Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, GA, USAJohn F Rawls - Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC, USALalita Ramakrishnan - Department of Microbiology, University of Washington, Seattle, WA, USA
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.327(5964), pp.466-469
- DOI
- 10.1126/science.1179663
- PMID
- 20007864
- PMCID
- PMC3125975
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Grant note
- R01 DK081426-02 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK K01 DK073695-02 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK K01 DK073695-03 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK K01 DK073695-04 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK R01 DK081426-01 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK K01 DK073695-01 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK R01 AI036396-19 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R01 AI054503-09 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Language
- English
- Date published
- 01/22/2010
- Academic Unit
- Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984093226402771
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