Downstream signals for MyD88-mediated phagocytosis of Borrelia burgdorferi can be initiated by TRIF and are dependent on PI3K.
Downstream signals for MyD88-mediated phagocytosis of Borrelia burgdorferi can be initiated by TRIF and are dependent on PI3K.
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DOI：
10.4049/jimmunol.0900724
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发表时间：
2009-07-01
期刊：
影响因子：
--
通讯作者：
Hu LT
中科院分区：
文献类型：
--
作者：
Shin OS;Miller LS;Modlin RL;Akira S;Uematsu S;Hu LT
我们以前已经表明，MyD 88是重要的摄取B。骨髓源性巨噬细胞（BMDM）对伯氏螺旋体的作用。MyD 88参与B摄取的机制。目前还没有很好地表征Burgdorferi。在这里，我们报告了MyD 88介导的B的吞噬缺陷。Burgdorferi可以通过MyD 88 −/−小鼠BMDM中的TLR 3/TRIF激活来补充。TLR 3/TRIF激活的这种作用不是由于其诱导I型干扰素，而是表明MyD 88和TRIF下游的信号传导途径的会聚。为了表征参与MyD 88介导的B吞噬作用的信号传导途径。Burgdorferi，用MAPK、PKC、JAK/STAT或PI 3 K的特异性抑制剂处理BMDM。仅抑制PI 3 K导致B显著降低。伯氏摄取与此一致，B。Burgdorferi激活MyD 88-或TLR 3-/TRIF-信号导致PI 3 K活性增加。此外，B.在MyD 88 −/− BMDM和PI 3 K抑制剂处理的BMDM中，与肌动蛋白相关蛋白（Arp 2/3）复合物的伯氏螺旋体（其在吞噬过程中促进肌动蛋白重排）类似地减少。综上所述，这些发现定义了一个必要的途径，其中来自MyD 88或TRIF的下游信号会聚在PI 3 K上，PI 3 K触发肌动蛋白聚合以启动B的吞噬作用。burgdorferi。
We previously have shown that MyD88 is important for uptake of B. burgdorferi by bone marrow derived macrophages (BMDMs). The mechanism by which MyD88 is involved in uptake of B. burgdorferi is currently is not well characterized. Here, we report that MyD88-mediated defect in the phagocytosis of B. burgdorferi can be complemented by TLR3/TRIF activation in BMDMs from MyD88−/− mice. This effect of TLR3/TRIF activation was not due to its induction of type I interferons, suggesting instead a convergence of signaling pathways downstream of MyD88 and TRIF. In order to characterize signaling pathways involved in MyD88-mediated phagocytosis of B. burgdorferi, BMDMs were treated with specific inhibitors of MAPK, PKC, JAK/STAT, or PI3K. Only inhibition of PI3K resulted in a significant decrease of B. burgdorferi uptake. Consistent with this, B. burgdorferi activation of MyD88- or TLR3-/TRIF-signaling resulted in increased activity of PI3K. In addition, association of B. burgdorferi with actin related protein (Arp2/3) complexes, which facilitate actin rearrangements during phagocytosis, was similarly reduced in MyD88−/− BMDMs and BMDMs treated with a PI3K inhibitor. Taken together, these findings define an essential pathway whereby downstream signals from MyD88 or TRIF converge on PI3K, which triggers actin polymerization to initiate the phagocytosis of B. burgdorferi.
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影响因子：
56.9
作者：
Blander, JM;Medzhitov, R
通讯作者：
Medzhitov, R
动力蛋白2是巨噬细胞中吞噬作用所必需的。
影响因子：
15.3
作者：
Gold, E S;Underhill, D M;Morrissette, N S;Guo, J;McNiven, M A;Aderem, A
通讯作者：
Aderem, A
DOI：
10.1084/jem.20031237
发表时间：
2004-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Doyle SE;O'Connell RM;Miranda GA;Vaidya SA;Chow EK;Liu PT;Suzuki S;Suzuki N;Modlin RL;Yeh WC;Lane TF;Cheng G
通讯作者：
Cheng G
影响因子：
30.5
作者：
Arbibe, L;Mira, JP;Knaus, UG
通讯作者：
Knaus, UG
影响因子：
3.1
作者：
HU, LT;PERIDES, G;KLEMPNER, MS
通讯作者：
KLEMPNER, MS