Caspase-11 protects against bacteria that escape the vacuole.

Caspase-11 protects against bacteria that escape the vacuole.
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caspase-11预防逃脱液泡的细菌。

DOI:
10.1126/science.1230751
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发表时间:
2013-02-22
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Miao EA
Miao EA
中科院分区:
其他
文献类型:
--
作者:
Aachoui Y;Leaf IA;Hagar JA;Fontana MF;Campos CG;Zak DE;Tan MH;Cotter PA;Vance RE;Aderem A;Miao EA

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半胱天冬酶是凋亡性的或炎性的。炎症性半胱天冬酶-1和-11触发焦亡,这是一种程序性细胞死亡。虽然两者在炎症性疾病中都是有害的,但只有Caspase-1在感染期间具有既定的保护作用。在此,我们报告,胱天蛋白酶-11所需的先天免疫细胞质,但不是空泡,细菌。虽然鼠伤寒沙门氏菌和嗜肺军团菌通常存在于空泡中,但异常进入胞质溶胶的特定突变体(分别为sifA和sdhA)触发了Caspase-11,增强了S.鼠伤寒沙门氏菌SifA体内。这种反应不需要NLRP 3、NLRC 4或ASC炎性体途径。自然侵入胞质溶胶的伯克霍尔德菌也触发了Caspase-11,保护小鼠免受B的致命攻击。thailandensis和B.假鼻疽因此,Caspase-11对于暴露于普遍存在的环境病原体的生存至关重要。
Caspases are either apoptotic or inflammatory. The inflammatory Caspases-1 and -11 trigger pyroptosis, a form of programmed cell death. Whereas both can be detrimental in inflammatory disease, only Caspase-1 has an established protective role during infection. Herein, we report that Caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria. While Salmonella typhimurium and Legionella pneumophila normally reside in the vacuole, specific mutants (sifA and sdhA, respectively) that aberrantly enter the cytosol triggered Caspase-11, enhancing clearance of S. typhimurium sifA in vivo. This response did not require NLRP3, NLRC4, or ASC inflammasome pathways. Burkholderia species that naturally invade the cytosol also triggered Caspase-11, protecting mice from lethal challenge with B. thailandensis and B. pseudomallei. Thus, Caspase-11 is critical for surviving exposure to ubiquitous environmental pathogens.
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