Mycobacteria target DC-SIGN to suppress dendritic cell function.
Mycobacteria target DC-SIGN to suppress dendritic cell function.
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DOI：
10.1084/jem.20021229
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发表时间：
2003-01-06
影响因子：
15.3
通讯作者：
van Kooyk, Y
中科院分区：
文献类型：
--
作者：
Geijtenbeek, TBH;van Vliet, SJ;Koppel, EA;Sanchez-Hernandez, M;Vandenbroucke-Grauls, CMJE;Appelmelk, B;van Kooyk, Y
结核分枝杆菌代表了一个世界性的健康风险和免疫抑制是一个特殊的问题，在M。肺结核感染。虽然巨噬细胞主要被感染，但树突状细胞（DC）在诱导针对M的细胞免疫应答中是重要的。结核我们假设DC代表M的靶点。结核病，并且观察到的免疫抑制由DC功能的调节引起。我们证明了DC特异性C型凝集素DC-SIGN是DC上的重要受体，其通过分枝杆菌细胞壁组分ManLAM捕获并内化完整的牛分枝杆菌卡介苗（BCG）。针对DC-SIGN阻断M的抗体。Bovis BCG感染的DC。ManLAM也由M.结核病感染的巨噬细胞，并已牵连作为一个毒力因子。引人注目的是，与DC-SIGN结合的ManLAM阻止分枝杆菌或LPS诱导的DC成熟。分枝杆菌和LPS均通过Toll样受体（TLR）信号传导诱导DC成熟，表明DC-SIGN在与ManLAM结合后干扰TLR介导的信号。针对DC-SIGN的阻断抗体逆转ManLAM介导的免疫抑制作用。我们的结果表明，M.结核病靶向DC-SIGN以感染DC并下调DC介导的免疫应答。此外，我们证明了DC-SIGN具有比以前更广泛的病原体识别谱，这表明DC-SIGN可能代表了HIV-1以外感染临床干预的分子靶点。
Mycobacterium tuberculosis represents a world-wide health risk and immunosuppression is a particular problem in M. tuberculosis infections. Although macrophages are primarily infected, dendritic cells (DCs) are important in inducing cellular immune responses against M. tuberculosis. We hypothesized that DCs represent a target for M. tuberculosis and that the observed immuno-suppression results from modulation of DC functions. We demonstrate that the DC-specific C-type lectin DC-SIGN is an important receptor on DCs that captures and internalizes intact Mycobacterium bovis bacillus Calmette-Guérin (BCG) through the mycobacterial cell wall component ManLAM. Antibodies against DC-SIGN block M. bovis BCG infection of DCs. ManLAM is also secreted by M. tuberculosis–infected macrophages and has been implicated as a virulence factor. Strikingly, ManLAM binding to DC-SIGN prevents mycobacteria- or LPS-induced DC maturation. Both mycobacteria and LPS induce DC maturation through Toll-like receptor (TLR) signaling, suggesting that DC-SIGN, upon binding of ManLAM, interferes with TLR-mediated signals. Blocking antibodies against DC-SIGN reverse the ManLAM-mediated immunosuppressive effects. Our results suggest that M. tuberculosis targets DC-SIGN both to infect DCs and to down-regulate DC-mediated immune responses. Moreover, we demonstrate that DC-SIGN has a broader pathogen recognition profile than previously shown, suggesting that DC-SIGN may represent a molecular target for clinical intervention in infections other than HIV-1.
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影响因子：
64.5
作者：
Geijtenbeek, TBH;Torensma, R;Figdor, CG
通讯作者：
Figdor, CG
影响因子：
4.4
作者：
Jiao, XN;Lo-Man, R;Leclerc, C
通讯作者：
Leclerc, C
影响因子：
56.9
作者：
Feinberg, H;Mitchell, DA;Weis, WI
通讯作者：
Weis, WI
影响因子：
4.4
作者：
Engering, A;Geijtenbeek, TBH;van Kooyk, Y
通讯作者：
van Kooyk, Y
DOI：
10.1084/jem.192.9.1213
发表时间：
2000-11-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jonuleit H;Schmitt E;Schuler G;Knop J;Enk AH
通讯作者：
Enk AH