DC-SIGN and CD150 have distinct roles in transmission of measles virus from dendritic cells to T-lymphocytes.
DC-SIGN and CD150 have distinct roles in transmission of measles virus from dendritic cells to T-lymphocytes.
复制标题
DOI：
10.1371/journal.ppat.1000049
复制
发表时间：
2008-04-18
期刊：
影响因子：
6.7
通讯作者：
Geijtenbeek, Teunis B. H.
中科院分区：
文献类型：
--
作者：
de Witte, Lot;de Vries, Rory D.;van der Vlist, Michiel;Yuksel, Selma;Litjens, Manja;de Swart, Rik L.;Geijtenbeek, Teunis B. H.
麻疹病毒（MV）是影响人类的最具传染性的病毒之一，通过呼吸道途径传播。在猕猴中，MV主要感染淋巴细胞和树突状细胞（DC）。关于MV感染的初始靶细胞知之甚少。由于DC桥接外周粘膜组织与淋巴组织，我们假设DC是在呼吸道中捕获MV并将病毒转运至淋巴组织的初始靶细胞，MV在淋巴组织中被传递至淋巴细胞。最近，我们已经证明，C型凝集素DC-SIGN与MV相互作用，并增强顺式DC的感染。使用免疫荧光显微镜，我们证明了DC-SIGN+ DC丰富地存在于呼吸道上皮细胞下方。DC-SIGN+ DC在体外通过CD 150或DC-SIGN摄取抗原后有效地将MV衍生的抗原呈递给CD 4 + T淋巴细胞。然而，DC-SIGN+ DC还介导MV向CD 4+和CD 8 + T淋巴细胞的传递。我们区分了两种不同的传播途径，依赖或独立于直接DC感染。DC-SIGN和CD 150均参与DC的直接感染和随后的从头合成病毒的传播。然而，DC-SIGN，而不是CD 150，介导MV向T淋巴细胞的转感染，独立于DC感染。总之，这些数据表明，在MV感染的启动，传播和清除过程中，DC的突出作用。尽管有有效的疫苗，麻疹病毒（MV）仍然是发展中国家儿童发病和死亡的主要原因。几乎所有未接种疫苗的儿童在MV爆发期间都会感染高度传染性病毒。这表明了原发感染的有效途径。然而，MV复制的主要靶细胞CD 150+淋巴细胞几乎不存在于MV进入体内的呼吸道中。在这里，我们证明了MV传播的另一种途径：大量存在于呼吸道上皮下组织中的树突状细胞可以通过与CD 150或DC-SIGN结合来捕获MV。虽然有些病毒颗粒被加工用于抗原呈递，但其他病毒颗粒则逃避降解。在病毒捕获后，DC迁移到淋巴组织，在那里它们遇到CD 150+淋巴细胞并传播病毒，之后开始病毒复制。我们的数据为麻疹病毒的传播提供了新的见解，并表明DC在麻疹发病机制中的双重作用。
Measles virus (MV) is among the most infectious viruses that affect humans and is transmitted via the respiratory route. In macaques, MV primarily infects lymphocytes and dendritic cells (DCs). Little is known about the initial target cell for MV infection. Since DCs bridge the peripheral mucosal tissues with lymphoid tissues, we hypothesize that DCs are the initial target cells that capture MV in the respiratory tract and transport the virus to the lymphoid tissues where MV is transmitted to lymphocytes. Recently, we have demonstrated that the C-type lectin DC-SIGN interacts with MV and enhances infection of DCs in cis. Using immunofluorescence microscopy, we demonstrate that DC-SIGN+ DCs are abundantly present just below the epithelia of the respiratory tract. DC-SIGN+ DCs efficiently present MV-derived antigens to CD4+ T-lymphocytes after antigen uptake via either CD150 or DC-SIGN in vitro. However, DC-SIGN+ DCs also mediate transmission of MV to CD4+ and CD8+ T-lymphocytes. We distinguished two different transmission routes that were either dependent or independent on direct DC infection. DC-SIGN and CD150 are both involved in direct DC infection and subsequent transmission of de novo synthesized virus. However, DC-SIGN, but not CD150, mediates trans-infection of MV to T-lymphocytes independent of DC infection. Together these data suggest a prominent role for DCs during the initiation, dissemination, and clearance of MV infection. Despite the availability of an effective vaccine, measles virus (MV) is still a major cause of childhood morbidity and mortality in developing countries. Almost all non-vaccinated children catch the highly contagious virus during an MV outbreak. This suggests an efficient route for primary infection. However, the main target cells for MV replication, CD150+ lymphocytes, are barely present in the respiratory tract where MV enters the body. Here we demonstrate an alternative route of MV transmission: dendritic cells that are abundantly present in the sub-epithelial tissues of the respiratory tract may capture MV through binding to either CD150 or DC-SIGN. Although some virus particles are processed for antigen presentation, others escape from degradation. After virus capture, DCs migrate to the lymphoid tissues where they encounter CD150+ lymphocytes and transmit the virus, after which viral replication is started. Our data provide new insights into the transmission of measles virus, and suggest a dual role for DCs in the pathogenesis of measles.
登录
查看更多内容
影响因子：
64.5
作者：
Geijtenbeek, TBH;Torensma, R;Figdor, CG
通讯作者：
Figdor, CG
影响因子：
5.4
作者：
Hashimoto, K;Ono, N;Yanagi, Y
通讯作者：
Yanagi, Y
影响因子：
3.7
作者：
RICHARDSON, CD;CHOPPIN, PW
通讯作者：
CHOPPIN, PW
影响因子：
5.4
作者：
Lee, B;Leslie, G;Doms, RW
通讯作者：
Doms, RW
影响因子：
4.4
作者：
Granelli-Piperno, A;Pritsker, A;Steinman, RM
通讯作者：
Steinman, RM