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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 1? 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.

SUBMITTER: Eklund D

PROVIDER: S-EPMC3923544 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Human gene variants linked to enhanced NLRP3 activity limit intramacrophage growth of Mycobacterium tuberculosis.

Eklund Daniel D Welin Amanda A Andersson Henrik H Verma Deepti D Söderkvist Peter P Stendahl Olle O Särndahl Eva E Lerm Maria M

The Journal of infectious diseases 20131024 5

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 inf ...[more]

PMID: 24158955

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