Deep-sequencing analysis of the mouse transcriptome response to infection with Brucella melitensis strains of differing virulence.
Deep-sequencing analysis of the mouse transcriptome response to infection with Brucella melitensis strains of differing virulence.
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DOI：
10.1371/journal.pone.0028485
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Bu Z
中科院分区：
文献类型：
--
作者：
Wang F;Hu S;Liu W;Qiao Z;Gao Y;Bu Z
羊种布氏杆菌是一种重要的人畜共患病原体，可引起布氏杆菌病，这种疾病影响羊、牛，偶尔也影响人类。B。羊种B. melitensis菌株M5-90，从B培养的减毒活疫苗。羊种布氏杆菌M28菌株在我国山羊和绵羊中已被用作控制布鲁氏菌病的有效工具。然而，导致B的毒力和致病性减弱的分子变化。人们对梅利滕斯的了解仍然很少。在这项研究中，我们采用Illumina基因组分析仪平台进行全基因组数字基因表达（DGE）分析小鼠腹腔巨噬细胞对B的反应。羊种感染在M28和M5-90感染的巨噬细胞中观察到基因表达谱的许多平行变化，表明它们采用相似的生存策略，特别是诱导抗炎和抗凋亡因子。此外，1019个差异表达的巨噬细胞转录物感染后4小时，不同的B。melitensis菌株，这些差异转录本显着确定参与溶酶体和丝裂原活化蛋白激酶（MAPK）途径的基因。进一步的分析采用基因本体（GO）分析：高富集测序鉴定了内吞作用、炎症、凋亡和转运途径。Path-Net和Signal-Net分析强调MAPK途径是关键的调控途径。此外，这些重要途径的关键差异表达基因均与糖尿病相关。这些发现证实了以前未被认识到的与B相关的基因转录变化。melitensis感染的巨噬细胞，这里确定的中央信号通路值得进一步研究。我们的数据为菌株M5-90的分子减毒机制提供了新的见解，并将有助于产生具有增强效力的新减毒疫苗株。
Brucella melitensis is an important zoonotic pathogen that causes brucellosis, a disease that affects sheep, cattle and occasionally humans. B. melitensis strain M5-90, a live attenuated vaccine cultured from B. melitensis strain M28, has been used as an effective tool in the control of brucellosis in goats and sheep in China. However, the molecular changes leading to attenuated virulence and pathogenicity in B. melitensis remain poorly understood. In this study we employed the Illumina Genome Analyzer platform to perform genome-wide digital gene expression (DGE) analysis of mouse peritoneal macrophage responses to B. melitensis infection. Many parallel changes in gene expression profiles were observed in M28- and M5-90-infected macrophages, suggesting that they employ similar survival strategies, notably the induction of anti-inflammatory and antiapoptotic factors. Moreover, 1019 differentially expressed macrophage transcripts were identified 4 h after infection with the different B. melitensis strains, and these differential transcripts notably identified genes involved in the lysosome and mitogen-activated protein kinase (MAPK) pathways. Further analysis employed gene ontology (GO) analysis: high-enrichment GOs identified endocytosis, inflammatory, apoptosis, and transport pathways. Path-Net and Signal-Net analysis highlighted the MAPK pathway as the key regulatory pathway. Moreover, the key differentially expressed genes of the significant pathways were apoptosis-related. These findings demonstrate previously unrecognized changes in gene transcription that are associated with B. melitensis infection of macrophages, and the central signaling pathways identified here merit further investigation. Our data provide new insights into the molecular attenuation mechanism of strain M5-90 and will facilitate the generation of new attenuated vaccine strains with enhanced efficacy.
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影响因子：
1.4
作者：
Cariaga-Martinez AE;Lorenzati MA;Riera MA;Cubilla MA;De La Rossa A;Giorgio EM;Tiscornia MM;Gimenez EM;Rojas ME;Chaneton BJ;Rodríguez DI;Zapata PD
通讯作者：
Zapata PD
影响因子：
3.1
作者：
Campos, MA;Rosinha, GMS;Oliveira, SC
通讯作者：
Oliveira, SC
影响因子：
11.4
作者：
Descargues, Pascal;Sil, Alok K.;Karin, Michael
通讯作者：
Karin, Michael
影响因子：
3.7
作者：
Chen F;He Y
通讯作者：
He Y
DOI：
10.3181/0904-rm-124
发表时间：
2009-12
期刊：
Experimental biology and medicine (Maywood, N.J.)
影响因子：
--
作者：
Covert J;Mathison AJ;Eskra L;Banai M;Splitter G
通讯作者：
Splitter G