Lethal inflammasome activation by a multidrug-resistant pathobiont upon antibiotic disruption of the microbiota.
Lethal inflammasome activation by a multidrug-resistant pathobiont upon antibiotic disruption of the microbiota.
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作者：
哺乳动物的肠道内有一个复杂的微生物群落，为宿主提供了许多益处。然而，微生物群也可以包括潜在的有毒物种，称为致病菌，当肠道内稳态被破坏时，它们可以引起疾病。致病菌致病的分子机制仍然知之甚少。在这里，我们描述了一种败血症样疾病，发生在肠道损伤后，在驱虫治疗的小鼠。脓毒症与一种特异性多药耐药大肠埃希菌的全身扩散有关。大肠杆菌病原体，在驱虫处理的小鼠的微生物群中急剧扩张。快速脓毒症样死亡需要先天免疫系统的一个组成部分，Naip 5-Nlrc 4炎性体。根据科赫的假设，我们找到了E。大肠杆菌致病菌足以激活Naip 5-Nlrc 4并在静脉内注射到未操作的小鼠中时引起疾病。这些发现揭示了先天免疫系统如何识别致病菌，从而导致脓毒症样疾病。
The mammalian intestine harbors a complex microbial community that provides numerous benefits to its host. However, the microbiota can also include potentially virulent species, termed pathobionts, which can cause disease when intestinal homeostasis is disrupted. The molecular mechanisms by which pathobionts cause disease remain poorly understood. Here we describe a sepsis-like disease that occurs upon gut injury in antibiotic-treated mice. Sepsis was associated with the systemic spread of a specific multidrug-resistant E. coli pathobiont that expanded dramatically in the microbiota of antibiotic-treated mice. Rapid sepsis-like death required a component of the innate immune system, the Naip5-Nlrc4 inflammasome. In accordance with Koch's postulates, we found the E. coli pathobiont was sufficient to activate Naip5-Nlrc4 and cause disease when injected intravenously into unmanipulated mice. These findings reveal how sepsis-like disease can result from recognition of pathobionts by the innate immune system.
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影响因子：
6.7
作者：
Henderson, Jeffrey P.;Crowley, Jan R.;Pinkner, Jerome S.;Walker, Jennifer N.;Tsukayama, Pablo;Stamm, Walter E.;Hooton, Thomas M.;Hultgren, Scott J.
通讯作者：
Hultgren, Scott J.
DOI：
10.1073/pnas.1016814108
发表时间：
2010-12-14
影响因子：
11.1
作者：
Hu, Bo;Elinav, Eran;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
64.5
作者：
Cadwell K;Patel KK;Maloney NS;Liu TC;Ng AC;Storer CE;Head RD;Xavier R;Stappenbeck TS;Virgin HW
通讯作者：
Virgin HW
DOI：
10.1084/jem.20100050
发表时间：
2010-05-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allen IC;TeKippe EM;Woodford RM;Uronis JM;Holl EK;Rogers AB;Herfarth HH;Jobin C;Ting JP
通讯作者：
Ting JP
影响因子：
64.8
作者：
Kofoed, Eric M.;Vance, Russell E.
通讯作者：
Vance, Russell E.