Salmonella Enteritidis GalE Protein Inhibits LPS-Induced NLRP3 Inflammasome Activation.
Salmonella Enteritidis GalE Protein Inhibits LPS-Induced NLRP3 Inflammasome Activation.
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肠炎沙门氏菌 GalE 蛋白抑制 LPS 诱导的 NLRP3 炎症小体激活
DOI：
10.3390/microorganisms10050911
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发表时间：
2022-04-26
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
微生物感染可以触发炎性小体的组装，促进细胞因子的分泌，如IL-1β和IL-18。众所周知，沙门氏菌可调节NLRC4(NLR家族卡区蛋白4)和NLRP3(NLR家族派林结构域3)炎症体的激活，然而沙门氏菌如何避免或延迟炎症体激活的机制尚不清楚。因此，我们利用肠炎沙门氏菌C50336Δ转座子文库来筛选调控炎性小体激活的基因。筛查显示半乳糖代谢相关基因Gale是炎症体激活所必需的。在这里，我们发现在感染ΔflicΔGale的J774A.1细胞或野生型骨髓源巨噬细胞(BMDM)中，与感染Δflic的细胞相比，炎症体的激活显著增加。重要的是，我们发现IL-1β的分泌是caspase-1依赖的，与典型的NLRP3炎症小体激活一致。此外，在小鼠模型中，ΔflicΔGale的毒力明显低于Δflic。最后，RNA-seq分析表明，与炎症小体相关的多个信号通路受到Gale的调控。综上所述，我们的结果表明Gale在沙门氏菌逃避炎性小体激活的调控网络中发挥了重要作用。
Microbial infection can trigger the assembly of inflammasomes and promote secretion of cytokines, such as IL-1β and IL-18. It is well-known that Salmonella modulates the activation of NLRC4 (NLR family CARD domain-containing protein 4) and NLRP3 (NLR family pyrin domain-containing 3) inflammasomes, however the mechanisms whereby Salmonella avoids or delays inflammasome activation remain largely unknown. Therefore, we used Salmonella Enteritidis C50336ΔfliC transposon library to screen for genes involved in modulating inflammasomes activation. The screen revealed the galactose metabolism-related gene galE to be essential for inflammasome activation. Here, we found that inflammasome activation was significantly increased in J774A.1 cells or wild-type bone marrow-derived macrophages (BMDMs) during infection by ΔfliCΔgalE compared to cells infected with ΔfliC. Importantly, we found that secretion of IL-1β was Caspase-1-dependent, consistent with canonical NLRP3 inflammasome activation. Furthermore, the virulence of ΔfliCΔgalE was significantly decreased compared to ΔfliC in a mouse model. Finally, RNA-seq analysis showed that multiple signaling pathways related to the inflammasome were subject to regulation by GalE. Taken together, our results suggest that GalE plays an important role in the regulatory network of Salmonella evasion of inflammasome activation.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
6.4
作者：
GILMAN, RH;HORNICK, RB;LIBONATI, JP
通讯作者：
LIBONATI, JP
影响因子：
4.4
作者：
Ferrari, Rafaela G.;Rosario, Denes K. A.;Conte-Junior, Carlos A.
通讯作者：
Conte-Junior, Carlos A.
影响因子：
3.2
作者：
Charpentier, X;Oswald, E
通讯作者：
Oswald, E
影响因子：
3.7
作者：
Eguale T;Gebreyes WA;Asrat D;Alemayehu H;Gunn JS;Engidawork E
通讯作者：
Engidawork E