title: Human gene variants linked to enhanced NLRP3 activity limit intramacrophage growth of Mycobacterium tuberculosis.
abstract: Activation of the NLRP3 inflammasome and subsequent generation of interleukin 1β is initiated in macrophages upon recognition of several stimuli. In the present work, we show that gain-of-function gene variants of inflammasome components known to predispose individuals to inflammatory disorders have a host-protective role during infection with Mycobacterium tuberculosis. By isolation of macrophages from patients and healthy blood donors with genetic variants in NLRP3 and CARD8 and subsequent infection of the cells with virulent M. tuberculosis, we show that these gene variants, combined, are associated with increased control of bacterial growth in human macrophages.
authors.affiliation: Division of Microbiology and Molecular Medicine.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eklund
authors.forename: Amanda
authors.initials: A
authors.lastname: Welin
authors.forename: Henrik
authors.initials: H
authors.lastname: Andersson
authors.forename: Deepti
authors.initials: D
authors.lastname: Verma
authors.forename: Peter
authors.initials: P
authors.lastname: Söderkvist
authors.forename: Olle
authors.initials: O
authors.lastname: Stendahl
authors.forename: Eva
authors.initials: E
authors.lastname: Särndahl
authors.forename: Maria
authors.initials: M
authors.lastname: Lerm
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000254:growth & development*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology
chemical_list: D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D009363:Neoplasm Proteins
keywords: C10X; CARD8; IL-1β; NLRP3; Q705K; human macrophage; inflammasome; mycobacteria; tuberculosis