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桃源行王安石翻译
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出门在外也不愁Toll-like receptor 9-dependent immune activation by unmethylated CpG motifs in Aspergillus fumigatus DNA.
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):2123-9. doi: 10.1128/IAI.00047-08. Epub
2008 Mar 10.Toll-like receptor 9-dependent immune activation by unmethylated CpG motifs in Aspergillus fumigatus DNA.1, , , , , , .1Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA 01605, USA.AbstractPhagocytic defenses are critical for effective host defenses against the opportunistic fungal pathogen Aspergillus fumigatus. Previous studies found that following challenge with A. fumigatus, Toll-like receptor 9 (TLR9) knockout mice survived longer than wild-type mice. However, the mechanism responsible was not defined. Here we demonstrate that A. fumigatus contains unmethylated CpG sequences, the natural ligands for TLR9. A. fumigatus DNA and synthetic CpG-rich oligodeoxynucleotides (ODNs) containing sequences found in the A. fumigatus genome potently stimulated the production of proinflammatory cytokines in mouse bone marrow-derived dendritic cells (BMDCs) and human plasmacytoid dendritic cells. The response was decreased when the fungal DNA was treated with a CpG methylase or with CpG-specific endonucleases. A role for TLR9 was demonstrated as cytokine production was abolished in BMDCs from TLR9-deficient mice. Moreover, transfection of HEK293 cells with human TLR9 conferred responsiveness to synthetic CpG-rich ODNs containing sequences found in A. fumigatus DNA. Taken together, these data demonstrate that TLR9 detects A. fumigatus DNA, resulting in the secretion of proinflammatory cytokines, which may contribute to the immune response to the pathogen.PMID:
[PubMed - indexed for MEDLINE] A. fumigatus DNA contains unmethylated CpG sequences. Genomic DNA was isolated from A. fumigatus and left untreated or treated with the indicated enzymes. “+” “-” indicates absence of treatment. The digest was then analyzed by 1% agarose gel electrophoresis with ethidium bromide staining. The left lane shows a DNA ladder with numbers indicating the size of the DNA, in kb. The figure is representative of 12 individual experiments, each with similar results.Infect Immun. ):.Stimulation of murine BMDCs by A. fumigatus DNA. BMDCs were stimulated by transfecting 2.5 μg/ml of A. fumigatus DNA or E. coli DNA that was left untreated (DNA) or treated with the CpG methyltransferase M.SssI (Meth DNA), MspI, or HpaII. CpG 1826 at 3 μg/ml served as a positive control, while unstimulated cells and GpC 2137 were negative controls. After 24 h, supernatants were collected and TNF-α (A) and IL-12p70 (B) concentrations were determined by ELISA. Data are means ± SE of five individual experiments. P was &0.001 according to one-way ANOVA with a Bonferroni posttest for TNF-α and IL-12p70 stimulated by untreated A. fumigatus or E. coli DNA compared with any treatment.Infect Immun. ):.A. fumigatus DNA stimulates TNF-α secretion in a TLR9-dependent manner. BMDCs from WT and TLR9-/- mice were transfected with the indicated concentrations of A. fumigatus DNA that was left untreated (Af DNA) or treated with the CpG methyltransferase M.SssI (Met Af DNA) and incubated at 37°C. After 24 h, supernatants were collected and TNF-α concentrations were determined by ELISA. The concentrations of TNF-α released from unstimulated WT and TLR9-/- BMDCs were 225 ± 40 pg/ml and 134 ± 18 pg/ml, respectively. Data are means ± SE of a representative (out of four) experiment performed in triplicate. P was &0.001 according to one-way ANOVA with a Bonferroni posttest for TNF-α stimulated by Af DNA in WT BMDCs compared with any other group at DNA concentrations of 3 and 10 μg/ml. DC, KO, knockout.Infect Immun. ):.Stimulation of human pDCs by A. fumigatus DNA. Human pDCs were isolated from PBMCs by positive selection using CD304+ magnetic beads. (A) pDCs were stimulated with 10 μg of A. fumigatus DNA which was either left untreated or methylated with the CpG methyltransferase M.SssI. Unstimulated and CpG 2336 (10 μg/ml)-stimulated pDCs served as negative and positive controls, respectively. After 18 to 24 h, supernatants were collected and analyzed by ELISA for IFN-α. Results are shown as means ± SE of seven individual donors. P was &0.001 comparing untreated and methylated DNA by one-way ANOVA with a Bonferroni posttest. (B) As in panel A, except a dose-response curve was performed comparing untreated and methylated A. fumigatus DNA. Data are means ± SE of a representative (out of three) experiment performed in triplicate. P was &0.001 comparing untreated and methylated DNA at concentrations of 1, 3, and 10 μg/ml by two-way ANOVA with a Bonferroni posttest.Infect Immun. ):.Stimulation of murine BMDCs by ODNs containing CpG-rich motifs present in the A. fumigatus genome. BMDCs from WT (top panel) and TLR9-/- (bottom panel) mice were stimulated with the indicated mouse-like CpG motifs (see Table S1 in the supplemental material). CpG 1826 served as a positive control, while unstimulated (Unstim) cells and GpC 2137 were negative controls. After 24 h, supernatants were collected and TNF-α concentrations were determined by ELISA. Data are means ± SE of a representative (out of three) experiment performed in triplicate.Infect Immun. ):.Stimulation of hTLR9-transfected HEK293 cells by ODNs containing CpG-rich motifs present in the A. fumigatus genome. HEK293 cells stably coexpressing hTLR9 and the NF-κB-driven luciferase reporter construct were stimulated with the indicated human-like CpG motifs (see Table S1 in the supplemental material). CpG 2007 served as a positive control, while GpC 2137 was a negative control. After 18 h, luciferase activity was determined in the cell lysates. Results are expressed as n-fold induction over unstimulated cells. Data are means ± SE of a representative (out of four) experiment performed in triplicate.Infect Immun. ):.Publication TypesMeSH TermsSubstancesGrant SupportFull Text SourcesOther Literature SourcesMolecular Biology Databases
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桃源行王安石翻译
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王维七言乐府诗《桃源行》将陶渊明叙事散文《桃花源记》改用诗歌形式表现出来,更调动了读者的想旦护测咎爻侥诧鞋超猫象力,颇为后人称道;还有同名诗词刘禹锡、王安石的“桃源行”也各具特色;初山微画雕《桃源行》则通过形象的画面来开拓诗境,“春来遍是桃花水,不辨仙源何处寻”,一种理想社会的迷茫意境给人留下了无穷的回味。
渔舟逐水爱山春,两岸桃花夹古津。
坐看红树不知远,行尽青溪忽值人。
山口潜行始隈隩,山开旷望旋平陆。
遥看一处攒云树,近入千家散花竹。
樵客初传汉姓名,居人未改秦衣服。
居人共住武陵源,还从物外起田园。
月明松下房栊静,日出云山鸡犬喧。
惊闻俗客争来集,竞引还家问都邑。
平明闾巷扫花开,薄暮渔樵乘水入。
初因避地去人间,及至成仙遂不还。
峡里谁知有人事,世中遥望空云山。
不疑灵境难闻见,尘心未尽思乡县。
山洞无论隔山水,辞家终拟长游衍。
自谓经过旧不迷,安知峰壑今来变。
当时只记入山深,青溪几度到云林。
春来遍是桃花水,不辨仙源何处寻。
物外:世外。
【简析】:
这首诗所写的内容源出陶渊明的《桃花源记》,但王维这首诗妙在毫无...
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