Macrophage-tropic HIV induces and exploits dendritic cell chemotaxis.
Macrophage-tropic HIV induces and exploits dendritic cell chemotaxis.
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DOI：
10.1084/jem.192.4.587
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发表时间：
2000-08-21
期刊：
影响因子：
--
通讯作者：
Austyn JM
中科院分区：
文献类型：
--
作者：
Lin CL;Sewell AK;Gao GF;Whelan KT;Phillips RE;Austyn JM
未成熟树突状细胞（iDC）表达CC趋化因子受体（CCR）5，其促进对激活调节的CC趋化因子、正常T细胞表达和分泌的（RANTES）、巨噬细胞炎性蛋白（MIP）-1α和MIP-1β的趋化性。相比之下，成熟DC下调CCR 5，但上调CXC趋化因子受体（CXCR）4，因此表现出对基质细胞衍生因子（SDF）-1α的趋化性增强。CCR 5和CXCR 4还分别作为嗜巨噬细胞（M-tropic）和嗜T细胞（T-tropic）人类免疫缺陷病毒（HIV）-1的辅助受体发挥作用。在这里，我们证明了iDC对M-嗜性（R5）而不是T-嗜性（X4）HIV-1的趋化性。此外，预先暴露于M嗜性HIV-1或其重组包膜蛋白可防止向CCR 5配体迁移。iDC向嗜M性HIV-1的迁移可增强DC-T细胞合胞体的形成，从而促进DC和辅助性T淋巴细胞的病毒产生和破坏。因此，DC趋化性的干扰HIV-1可能有助于在原发性感染和艾滋病的免疫抑制。此外，iDC向HIV-1的迁移可能有助于通过丰富的DC细胞表面蛋白DC特异性细胞间粘附分子（ICAM）3-抓取非整联蛋白（DC-SIGN）捕获R5 HIV-1病毒粒子。与DC细胞特异性DC-SIGN结合的HIV-1保留了数天感染反式复制许可T细胞的能力。因此，HIV-1对DC的募集可以联合收割机与DC-SIGN捕获病毒并将其传递给T细胞的能力相结合，从而促进病毒在感染个体内的传播。
Immature dendritic cells (iDCs) express the CC chemokine receptor (CCR)5, which promotes chemotaxis toward the CC chemokines regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α, and MIP-1β. By contrast, mature DCs downregulate CCR5 but upregulate CXC chemokine receptor (CXCR)4, and as a result exhibit enhanced chemotaxis toward stromal cell–derived factor (SDF)-1α. CCR5 and CXCR4 also function as coreceptors for macrophage-tropic (M-tropic) and T cell–tropic (T-tropic) human immunodeficiency virus (HIV)-1, respectively. Here, we demonstrate chemotaxis of iDCs toward M-tropic (R5) but not T-tropic (X4) HIV-1. Furthermore, preexposure to M-tropic HIV-1 or its recombinant envelope protein prevents migration toward CCR5 ligands. The migration of iDCs toward M-tropic HIV-1 may enhance formation of DC–T cell syncytia, thus promoting viral production and destruction of both DC and T helper lymphocytes. Therefore, disturbance of DC chemotaxis by HIV-1 is likely to contribute to immunosuppression in primary infection and AIDS. In addition, migration of iDCs toward HIV-1 may aid the capture of R5 HIV-1 virions by the abundant DC cell surface protein DC-specific intercellular adhesion molecule (ICAM)3-grabbing nonintegrin (DC-SIGN). HIV-1 bound to DC cell–specific DC-SIGN retains the ability to infect replication-permissive T cells in trans for several days. Consequently, recruitment of DC by HIV-1 could combine with the ability of DC-SIGN to capture and transmit the virus to T cells, and so facilitate dissemination of virus within an infected individual.
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影响因子：
64.5
作者：
Geijtenbeek, TBH;Torensma, R;Figdor, CG
通讯作者：
Figdor, CG
DOI：
10.1073/pnas.97.7.3382
发表时间：
2000-03-28
影响因子：
11.1
作者：
Oxenius, A;Price, DA;Phillips, RE
通讯作者：
Phillips, RE
影响因子：
56.9
作者：
Feng, Y;Broder, CC;Berger, EA
通讯作者：
Berger, EA
影响因子：
5.4
作者：
LAYNE, SP;MERGES, MJ;NARA, PL
通讯作者：
NARA, PL
影响因子：
9.2
作者：
Price, DA;Sewell, AK;Phillips, RE
通讯作者：
Phillips, RE