Salmonella small RNA fragment Sal-1 facilitates bacterial survival in infected cells via suppressing iNOS induction in a microRNA manner.
Salmonella small RNA fragment Sal-1 facilitates bacterial survival in infected cells via suppressing iNOS induction in a microRNA manner.
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沙门氏菌小 RNA 片段 Sal-1 通过以 microRNA 方式抑制 iNOS 诱导，促进感染细胞中细菌的存活
DOI：
10.1038/s41598-017-17205-4
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发表时间：
2017-12-05
影响因子：
4.6
通讯作者：
Gu H
中科院分区：
文献类型：
--
作者：
Zhao C;Zhou Z;Zhang T;Liu F;Zhang CY;Zen K;Gu H
沙门氏菌可以劫持宿主的非典型miRNA加工机制，将其小的非编码RNA切割成约22-nt的RNA片段Sal-1，这有助于沙门氏菌在感染宿主中的存活。然而，Sal-1促进沙门氏菌存活的机制仍然未知。在本研究中，我们报道了Sal-1以miRNA方式靶向细胞诱导型一氧化氮合酶（iNOS），导致宿主细胞iNOS/NO介导的抗微生物能力减弱。首先，沙门氏菌感染的上皮细胞中Sal-1的耗竭显著增加了iNOS水平，但不增加各种炎性细胞因子的水平。生物信息学分析和诱变策略与人和小鼠中作为Sal-1靶点的iNOS mRNA的鉴定一致。其次，蛋白质印迹和免疫组化分析证实，Sal-1抑制iNOS的表达在体外和体内，从而减少NO的产生。最后，Sal-1促进沙门氏菌的生存，通过抑制诱导型一氧化氮合酶诱导在小鼠模型中通过表达突变的诱导型一氧化氮合酶，这不是由Sal-1在小鼠结肠中的目标。总之，我们的研究为胞内细菌调节宿主天然免疫反应的致病机制提供了新的见解。
Salmonella can hijack host atypical miRNA processing machinery to cleave its small non-coding RNA into a ~22-nt RNA fragment, Sal-1, which facilitates Salmonella survival in the infected host. The mechanism through which Sal-1 promotes Salmonella survival, however, remains unknown. In the present study, we reported that Sal-1 targets cellular inducible nitric oxide synthase (iNOS) in a miRNA manner, leading to attenuation of host cell iNOS/NO-mediated anti-microbial capacity. First, depletion of Sal-1 in Salmonella-infected epithelial cells significantly increased the iNOS level but not the levels of various inflammatory cytokines. Bioinformatics analysis and mutagenesis strategies were consistent with the identification of mRNA of iNOS as a target of Sal-1 in both human and mice. Second, western blot and immunohistochemical analysis confirmed that Sal-1 suppressed iNOS expression in vitro and in vivo, thus reducing the production of NO. Finally, Sal-1 facilitating Salmonella survival through suppressing iNOS induction was confirmed in mouse model by expressing mutated iNOS that is not targeted by Sal-1 in mice colon. In conclusion, our study provides new insight into the pathogenic mechanism of intracellular bacteria to modulate host innate immune response.
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影响因子：
15.3
作者：
Mastroeni, P;Vazquez-Torres, A;Fang, F C;Xu, Y;Khan, S;Hormaeche, C E;Dougan, G
通讯作者：
Dougan, G
影响因子：
4.8
作者：
Bang, Iel-Soo;Liu, Limin;Fang, Ferric C.
通讯作者：
Fang, Ferric C.
影响因子：
24.5
作者：
Forte, P;Dykhuizen, RS;Benjamin, N
通讯作者：
Benjamin, N
影响因子：
10.5
作者：
Skalsky RL;Cullen BR
通讯作者：
Cullen BR
沙门氏菌在受感染的细胞中产生类似 microRNA 的 RNA 片段 Sal-1 以促进细胞内存活
影响因子：
4.6
作者：
Gu H;Zhao C;Zhang T;Liang H;Wang XM;Pan Y;Chen X;Zhao Q;Li D;Liu F;Zhang CY;Zen K
通讯作者：
Zen K