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Open Access Green as soon as Postprint is submitted to ZB.
Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis.
Eur. J. Immunol. 42, 374-384 (2012)
As a hallmark of tuberculosis (TB), Mycobacterium tuberculosis (MTB) induces granulomatous lung lesions and systemic inflammatory responses during active disease. Molecular regulation of inflammation is associated with inflammasome assembly. We determined the extent to which MTB triggers inflammasome activation and how this impacts on the severity of TB in a mouse model. MTB stimulated release of mature IL-1β in macrophages while attenuated M. bovis BCG failed to do so. Tubercle bacilli specifically activated the NLRP3 inflammasome and this propensity was strictly controlled by the virulence-associated RD1 locus of MTB. However, Nlrp3-deficient mice controlled pulmonary TB, a feature correlated with NLRP3-independent production of IL-1β in infected lungs. Our studies demonstrate that MTB activates the NLRP3 inflammasome in macrophages in an ESX-1-dependent manner. However, during TB, MTB promotes NLRP3- and caspase-1-independent IL-1β release in myeloid cells recruited to lung parenchyma and thus overcomes NLRP3 deficiency in vivo in experimental models.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
ESX-1 secretion system; Inflammasome; IL-1β; Mycobacterium tuberculosis; NLRP3
ISSN (print) / ISBN
0014-2980
e-ISSN
1521-4141
Journal
European Journal of Immunology
Quellenangaben
Volume: 42,
Issue: 2,
Pages: 374-384
Publisher
Wiley
Publishing Place
Hoboken
Reviewing status
Peer reviewed