TLR2 activation enhances HIV nuclear import and infection through T cell activation-independent and -dependent pathways.
TLR2 activation enhances HIV nuclear import and infection through T cell activation-independent and -dependent pathways.
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DOI：
10.4049/jimmunol.1102098
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发表时间：
2012-02-01
期刊：
影响因子：
--
通讯作者：
Chang TL
中科院分区：
文献类型：
--
作者：
Ding J;Chang TL
TLR 2激活在淋病奈瑟菌介导的HIV感染静息CD 4 + T细胞的增强中起关键作用。我们研究了TLR 2增强HIV作用的信号通路。TLR 2而不是IL-2信号促进HIV核输入;然而，这两种信号都是最大效果所必需的。虽然TLR 2信号不能激活T细胞，但它增加了IL-2诱导的T细胞活化。环孢菌素A（CsA）和IkBa抑制剂阻断TLR 2介导的HIV感染/核输入增强。PI 3 K抑制剂阻断HIV感染/核输入和T细胞活化，并对TLR 2/ IL-2激活的CD 4 + T细胞的细胞周期进程产生中度抑制作用。阻断p38信号传导抑制TLR 2介导的HIV核输入/感染增强。然而，p38抑制剂对T细胞活化和TCR/CD 3介导的HIV感染/核输入增强没有显著影响。细胞周期阻滞剂aphidicolin（APH）阻断TLR 2和TCR/CD 3诱导的HIV感染/核输入。最后，CsA和IκBα和PI 3 K抑制剂阻断了TLR 2介导的IκBα磷酸化，但p38抑制剂不能。我们的研究结果表明，TLR 2激活增强HIV感染/核输入静息CD 4 + T细胞通过T细胞活化依赖和独立的机制。
TLR2 activation plays a crucial role in Neisseria gonorrhoeae-mediated enhancement of HIV infection of resting CD4+ T cells. We examined signaling pathways involved in the HIV enhancing effect of TLR2. TLR2 but not IL-2 signals promoted HIV nuclear import; however, both signals were required for the maximal effect. Although TLR2 signaling could not activate T cells, it increased IL-2-induced T cell activation. Cyclosporin A (CsA) and IkBa inhibitor blocked TLR2-mediated enhancement of HIV infection/nuclear import. PI3K inhibitor blocked HIV infection/nuclear import and T cell activation, and exerted a moderate inhibitory effect on cell cycle progression in CD4+ T cells activated by TLR2/ IL-2. Blockade of p38 signaling suppressed TLR2-mediated enhancement of HIV nuclear import/ infection. However, the p38 inhibitor did not have a significant effect on T cell activation nor TCR/CD3-mediated enhancement of HIV infection/nuclear import. The cell cycle arresting reagent aphidicolin (APH) blocked TLR2- and TCR/CD3-induced HIV infection/ nuclear import. Finally, CsA and IκBα and PI3K inhibitors but not the p38 inhibitor blocked TLR2-mediated IκBα phosphorylation. Our results suggest that TLR2 activation enhances HIV infection/nuclear import in resting CD4+ T cells through both T cell activation dependent and independent mechanisms.
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