Role of SPI-1 secreted effectors in acute bovine response to Salmonella enterica Serovar Typhimurium: a systems biology analysis approach.
Role of SPI-1 secreted effectors in acute bovine response to Salmonella enterica Serovar Typhimurium: a systems biology analysis approach.
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DOI：
10.1371/journal.pone.0026869
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Adams LG
中科院分区：
文献类型：
--
作者：
Lawhon SD;Khare S;Rossetti CA;Everts RE;Galindo CL;Luciano SA;Figueiredo JF;Nunes JE;Gull T;Davidson GS;Drake KL;Garner HR;Lewin HA;Bäumler AJ;Adams LG
沙门氏菌（Salmonella enterica Serovar Typhimurium）鼠伤寒沙门氏菌（Typhimurium）引起小肠结肠炎，伴有腹泻和多形核白细胞（PMN）流入人类和小牛的肠粘膜。在致病性岛I编码的沙门氏菌III型分泌系统（T3SS）将沙门氏菌效应蛋白SipA、SopA、SopB、SopD和SopE2转运到上皮细胞中，并且是诱导腹泻所需的。这些效应蛋白共同作用以诱导肠液分泌和C-X-C趋化因子的转录，将PMN募集到感染部位。虽然已经表征了效应物与培养的宿主细胞的单个分子相互作用，但它们在肠液分泌和炎症中的组合作用尚不清楚。我们假设，牛肠粘膜对野生型沙门氏菌和SiPA，SopABDE 2效应突变体相对于未感染的牛回肠的反应的比较将揭示迄今为止未鉴定的沙门氏菌相关的宿主细胞途径。为了确定这些毒力因子的协同作用，使用牛回肠环结扎模型来测量对野生型S.鼠伤寒沙门氏菌（WT）和Δ sipA，sopABDE 2突变体（MUT）在感染12小时内使用牛微阵列。使用标准微阵列分析和动态贝叶斯网络建模方法（DBN）分析数据。这两种分析方法都证实了沙门氏菌感染的免疫应答基因表达增加和新基因表达。基因表达变化映射到219个分子相互作用途径和1620个基因本体组。贝叶斯网络建模确定了感染对几种相互关联的信号传导途径的影响，包括MAPK、磷脂酰肌醇、mTOR、钙、Toll样受体、CCR3、Wnt、TGF-β和肌动蛋白细胞骨架的调节以及用于模拟宿主-病原体相互作用的细胞凋亡。WT和MUT的比较表明，在感染的早期时间点（15分钟、30分钟和1小时），在磷脂酰肌醇、CCR3、Wnt和TGF-β信号通路以及肌动蛋白细胞骨架通路的调节中，宿主应答的模式显著不同。
Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis with diarrhea and polymorphonuclear cell (PMN) influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS) encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrhea-associated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT) and a ΔsipA, sopABDE2 mutant (MUT) across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic Bayesian network modeling approach (DBN). Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-β, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host-pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response at early time points of infection (15 minutes, 30 minutes and one hour) within phosphatidylinositol, CCR3, Wnt, and TGF-β signaling pathways and the regulation of actin cytoskeleton pathway.
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影响因子：
6.7
作者：
Bruno VM;Hannemann S;Lara-Tejero M;Flavell RA;Kleinstein SH;Galán JE
通讯作者：
Galán JE
影响因子：
5.3
作者：
AEBI, M;FAH, J;STAEHELI, P
通讯作者：
STAEHELI, P
DOI：
10.1084/jem.139.5.1189
发表时间：
1974-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carter PB;Collins FM
通讯作者：
Collins FM
影响因子：
3.6
作者：
FRANCIS, CL;STARNBACH, MN;FALKOW, S
通讯作者：
FALKOW, S
影响因子：
3.4
作者：
Bakowski, Malina A.;Cirulis, Judith T.;Brumell, John H.
通讯作者：
Brumell, John H.