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http://purl.uniprot.org/citations/20148899http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20148899http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20148899http://www.w3.org/2000/01/rdf-schema#comment"Interleukin-1beta (IL-1beta) represents one of the most important mediators of inflammation and host responses to infection. Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, induces IL-1beta secretion at the site of infection, but the underlying mechanism(s) are poorly understood. In this work we show that Mtb infection of macrophages stimulates caspase-1 activity and promotes the secretion of IL-1beta. This stimulation requires live intracellular bacteria expressing a functional ESX-1 secretion system. ESAT-6, an ESX-1 substrate implicated in membrane damage, is both necessary and sufficient for caspase-1 activation and IL-1beta secretion. ESAT-6 promotes the access of other immunostimulatory agents such as AG85 into the macrophage cytosol, indicating that this protein may contribute to caspase-1 activation largely by perturbing host cell membranes. Using a high-throughput shRNA-based screen we found that numerous NOD-like receptors (NLRs) and CARD domain-containing proteins (CARDs) were important for IL-1beta secretion upon Mtb infection. Most importantly, NLRP3, ASC and caspase-1 form an infection-inducible inflammasome complex that is essential for IL-1beta secretion. In summary, we show that recognition of Mtb infection by the NLRP3 inflammasome requires the activity of the bacterial virulence factor ESAT-6, and the subsequent IL-1beta response is regulated by a number of NLR/CARD proteins."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.org/dc/terms/identifier"doi:10.1111/j.1462-5822.2010.01450.x"xsd:string
http://purl.uniprot.org/citations/20148899http://purl.org/dc/terms/identifier"doi:10.1111/j.1462-5822.2010.01450.x"xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Griffiths G."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Griffiths G."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Anes E."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Anes E."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Hacohen N."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Hacohen N."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Mishra B.B."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Mishra B.B."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Moita L.F."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Moita L.F."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Moura-Alves P."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Moura-Alves P."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Sonawane A."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/author"Sonawane A."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/name"Cell. Microbiol."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/name"Cell. Microbiol."xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/pages"1046-1063"xsd:string
http://purl.uniprot.org/citations/20148899http://purl.uniprot.org/core/pages"1046-1063"xsd:string