Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis.

Détails

ID Serval
serval:BIB_AA9A80A8B5F2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Activation of the NLRP3 inflammasome by Mycobacterium tuberculosis is uncoupled from susceptibility to active tuberculosis.
Périodique
European Journal of Immunology
Auteur⸱e⸱s
Dorhoi A., Nouailles G., Jörg S., Hagens K., Heinemann E., Pradl L., Oberbeck-Müller D., Duque-Correa M.A., Reece S.T., Ruland J., Brosch R., Tschopp J., Gross O., Kaufmann S.H.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Statut éditorial
Publié
Date de publication
2012
Volume
42
Numéro
2
Pages
374-384
Langue
anglais
Résumé
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.
Mots-clé
Animals, Carrier Proteins/genetics, Carrier Proteins/immunology, Disease Models, Animal, Disease Progression, Disease Susceptibility, Homeodomain Proteins/metabolism, Humans, Inflammasomes/immunology, Interleukin-1beta/metabolism, Lung/pathology, Macrophages/immunology, Macrophages/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mycobacterium tuberculosis/immunology, Mycobacterium tuberculosis/pathogenicity, Proto-Oncogene Proteins/metabolism, Transcription Factors/metabolism, Tuberculosis, Pulmonary/immunology, Tuberculosis, Pulmonary/physiopathology, Vaccines, Attenuated, Virulence
Pubmed
Web of science
Création de la notice
07/12/2012 10:24
Dernière modification de la notice
20/08/2019 15:14
Données d'usage