Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy.
Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy.
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DOI：
10.1371/journal.pone.0064748
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Moraes MO
中科院分区：
文献类型：
--
作者：
Guerreiro LT;Robottom-Ferreira AB;Ribeiro-Alves M;Toledo-Pinto TG;Rosa Brito T;Rosa PS;Sandoval FG;Jardim MR;Antunes SG;Shannon EJ;Sarno EN;Pessolani MC;Williams DL;Moraes MO
在此，我们在感染活M.麻风，并确定了新的差异表达基因（DEG）在M。麻风病感染细胞同时，我们在遗传学研究和生物学实验中选择了与麻风病相关或有牵连的候选基因。通过多重qPCR在两种独立类型的样品中选择47个基因进行验证。首先，使用THP-1细胞的体外模型用活麻风分枝杆菌和M.牛卡介苗（BCG）。在第二种情况下，测试了从麻风病或其他周围神经病患者的神经活检中获得的mRNA。我们检测到了区分M的DEG。牛卡介苗（M. bovis BCG）;麻风病感染M后敏感反应的特定特征。当与BCG相比时，麻风感染导致包括CCL 2、CCL 3、IL 8和SOD 2基因的抑制。在神经活检中筛选了相同的47个基因集，这证实了麻风病中CCL 2和CCL 3的下调，但也证明了参与线粒体代谢的基因的下调，以及参与脂质代谢和泛素化的基因的上调。最后，在确诊为麻风病的患者中鉴定了DEG的基因表达特征。分类树能够确定80%的情况下，麻风或非麻风周围神经病变的基础上表达的LDLR和CCL 4。一般的免疫和线粒体低反应状态发生在响应M。麻风病感染此外，最重要的基因和途径也得到了强调，为麻风病的早期诊断和治疗提供了新的工具。
Herein, we performed microarray experiments in Schwann cells infected with live M. leprae and identified novel differentially expressed genes (DEG) in M. leprae infected cells. Also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. Forty-seven genes were selected for validation in two independent types of samples by multiplex qPCR. First, an in vitro model using THP-1 cells was infected with live Mycobacterium leprae and M. bovis bacillus Calmette-Guérin (BCG). In a second situation, mRNA obtained from nerve biopsies from patients with leprosy or other peripheral neuropathies was tested. We detected DEGs that discriminate M. bovis BCG from M. leprae infection. Specific signatures of susceptible responses after M. leprae infection when compared to BCG lead to repression of genes, including CCL2, CCL3, IL8 and SOD2. The same 47-gene set was screened in nerve biopsies, which corroborated the down-regulation of CCL2 and CCL3 in leprosy, but also evidenced the down-regulation of genes involved in mitochondrial metabolism, and the up-regulation of genes involved in lipid metabolism and ubiquitination. Finally, a gene expression signature from DEG was identified in patients confirmed of having leprosy. A classification tree was able to ascertain 80% of the cases as leprosy or non-leprous peripheral neuropathy based on the expression of only LDLR and CCL4. A general immune and mitochondrial hypo-responsive state occurs in response to M. leprae infection. Also, the most important genes and pathways have been highlighted providing new tools for early diagnosis and treatment of leprosy.
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影响因子：
5.3
作者：
Alter A;de Léséleuc L;Van Thuc N;Thai VH;Huong NT;Ba NN;Cardoso CC;Grant AV;Abel L;Moraes MO;Alcaïs A;Schurr E
通讯作者：
Schurr E
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
6.4
作者：
Grant, Audrey V.;Alter, Andrea;Alcais, Alexandre
通讯作者：
Alcais, Alexandre
影响因子：
56.9
作者：
Liu, PT;Stenger, S;Modlin, RL
通讯作者：
Modlin, RL
影响因子：
168.9
作者：
Fine, PEM;Ponnighaus, JM;Peto, R
通讯作者：
Peto, R