Division of Microbiology and Molecular Medicine.
J Infect Dis. 2014 Mar 1;209(5):749-53. doi: 10.1093/infdis/jit572. Epub 2013 Oct 24.
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.
NLRP3 炎性小体的激活以及随后白细胞介素 1β 的产生，是在巨噬细胞识别几种刺激物后开始的。在本工作中，我们表明，已知易患炎症性疾病的炎性小体成分的功能获得性基因突变，在感染结核分枝杆菌时具有宿主保护作用。通过从携带 NLRP3 和 CARD8 基因突变的患者和健康献血者中分离巨噬细胞，并随后用毒力结核分枝杆菌感染这些细胞，我们表明这些基因突变的组合与人类巨噬细胞中细菌生长的控制增加有关。
