Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome.
Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome.
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DOI：
10.1016/j.immuni.2011.05.016
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发表时间：
2011-08-26
期刊：
影响因子：
32.4
通讯作者：
Golenbock DT
中科院分区：
文献类型：
--
作者：
Sharma S;DeOliveira RB;Kalantari P;Parroche P;Goutagny N;Jiang Z;Chan J;Bartholomeu DC;Lauw F;Hall JP;Barber GN;Gazzinelli RT;Fitzgerald KA;Golenbock DT
虽然Toll样受体9（TLR 9）已被牵连在调节细胞因子和I型干扰素（IFN）的生产过程中疟疾在人类和小鼠，恶性疟原虫基因组的高AT含量促使我们研究疟疾DNA触发TLR 9独立的DNA传感途径的可能性。在恶性疟原虫的基因组中存在超过6000个ATTTTTAC（“富含AT”）基序，我们在此显示其有效地诱导I型IFN。寄生虫DNA、寄生红细胞和含有AT-r基序的寡核苷酸通过不涉及先前描述的传感器（包括TLR 9、DAI、RNA聚合酶-III或IFI 16/p204）的途径诱导I型IFN。相反，富含AT的DNA传感涉及与STING、TBK 1和IRF 3-IRF 7信号通路偶联的未知受体。缺乏IRF 3和IRF 7、激酶TBK 1或I型IFN受体的小鼠对致命的脑型疟疾具有抗性。总的来说，这些观察结果暗示了在恶性疟原虫疟疾中通过STING、TBK 1和IRF 3-IRF 7的富含AT的DNA传感。
Although Toll-like receptor 9 (TLR9) has been implicated in regulating cytokine and type I interferon (IFN) production during malaria in humans and mice, the high AT content of the Plasmodium falciparum genome prompted us to examine the possibility that malarial DNA triggered TLR9-independent DNA sensing pathways. Over 6000 ATTTTTAC (“AT-rich”) motifs are present in the genome of P. falciparum, which we show here potently induce type I IFNs. Parasite DNA, parasitized erythrocytes and oligonucleotides containing the AT-r motif induce type I IFNs via a pathway that did not involve previously described sensors including TLR9, DAI, RNA polymerase-III or IFI16/p204. Rather, AT-rich DNA sensing involved an unknown receptor that coupled to STING, TBK1 and IRF3-IRF7 signaling pathway. Mice lacking both IRF3 and IRF7, the kinase TBK1 or the type I IFN receptor were resistant to otherwise lethal cerebral malaria. Collectively, these observations implicate AT-rich DNA sensing via STING, TBK1 and IRF3-IRF7 in P. falciparum malaria.
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影响因子：
64.5
作者：
Dixit E;Boulant S;Zhang Y;Lee AS;Odendall C;Shum B;Hacohen N;Chen ZJ;Whelan SP;Fransen M;Nibert ML;Superti-Furga G;Kagan JC
通讯作者：
Kagan JC
影响因子：
11.4
作者：
Bonnard, M;Mirtsos, C;Yeh, WC
通讯作者：
Yeh, WC
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1073/pnas.0809742106
发表时间：
2009-04-07
影响因子：
11.1
作者：
Franklin, Bernardo S.;Parroche, Peggy;Gazzinelli, Ricardo T.
通讯作者：
Gazzinelli, Ricardo T.