Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis.
Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis.
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DOI：
10.1111/j.1462-5822.2011.01643.x
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发表时间：
2011-10
影响因子：
3.4
通讯作者：
Monack D
中科院分区：
文献类型：
--
作者：
Peng K;Broz P;Jones J;Joubert LM;Monack D
细胞内细菌病原体新杀弗朗西斯菌和活疫苗株（LVS）在巨噬细胞胞质溶胶中被AIM 2炎性体识别，这导致半胱天冬酶-1活化以及活性IL-1β、IL-18的加工和分泌和细胞凋亡。已有研究报道F.特定基因中的novicida和LVS突变体（例如，FTT 0584、mviN和ripA）在宿主细胞中诱导升高的炎性体活化和高细胞毒性，导致F.杀novicida和LVS可能具有主动调节炎性小体活化的蛋白质。然而，没有直接证据表明这种炎性小体逃避机制。在这里，我们首次证明了上述突变体，沿着广泛的F。缺乏膜相关蛋白（Δ FTT 0584、ΔmviN、ΔripA、ΔfopA和Δ FTN 1217）或缺乏参与O-抗原或LPS生物合成的基因（ΔwbtA和ΔlpxH）的杀线虫超细胞毒性突变体更多地在细胞内裂解，从而激活增加水平的AIM 2依赖性焦亡和其他先天免疫信号传导途径。这表明在F. novicida和LVS.此外，未来的研究可能需要考虑增加细菌溶解作为一个可能的原因时，蛋白质组成或细菌膜的表面碳水化合物被改变的多种先天免疫途径的刺激升高。
Intracellular bacterial pathogens Francisella novicida and the Live Vaccine Strain (LVS) are recognized in the macrophage cytosol by the AIM2 inflammasome, which leads to the activation of caspase-1 and the processing and secretion of active IL-1β, IL-18 and pyroptosis. Previous studies have reported that F. novicida and LVS mutants in specific genes (e.g., FTT0584, mviN and ripA) induce elevated inflammasome activation and hypercytotoxicity in host cells, leading to the proposal that F. novicida and LVS may have proteins that actively modulate inflammasome activation. However, there has been no direct evidence of such inflammasome evasion mechanisms. Here, we demonstrate for the first time that the above mutants, along with a wide range of F. novicida hypercytotoxic mutants that are deficient for membrane-associated proteins (ΔFTT0584, ΔmviN, ΔripA, ΔfopA and ΔFTN1217) or deficient for genes involved in O-antigen or LPS biosynthesis (ΔwbtA and ΔlpxH) lyse more intracellularly, thus activating increased levels of AIM2-dependent pyroptosis and other innate immune signaling pathways. This suggests that an inflammasome-specific evasion mechanism may not be present in F. novicida and LVS. Furthermore, future studies may need to consider increased bacterial lysis as a possible cause of elevated stimulation of multiple innate immune pathways when the protein composition or surface carbohydrates of the bacterial membrane is altered.
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影响因子：
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作者：
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影响因子：
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影响因子：
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作者：
Henry, Thomas;Brotcke, Anna;Weiss, David S.;Thompson, Lucinda J.;Monack, Denise M.
通讯作者：
Monack, Denise M.
DOI：
10.1073/pnas.0601838103
发表时间：
2006-09-26
影响因子：
11.1
作者：
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通讯作者：
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