The β-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria
The β-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria
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DOI：
10.1182/blood-2006-05-024406
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发表时间：
2006-11-01
期刊：
影响因子：
20.3
通讯作者：
Schorey, Jeffrey S.
中科院分区：
文献类型：
--
作者：
Yadav, Mahesh;Schorey, Jeffrey S.
模式识别受体（PRRs）在巨噬细胞对分枝杆菌感染的反应中起重要作用。然而，这些受体如何协同工作以促进这种巨噬细胞反应仍不清楚。在这项研究中，我们使用从甘露糖受体（MR），补体受体3（CR 3），MyD 88，Toll样受体4（TLR 4）和TLR 2敲除小鼠中分离的骨髓源性巨噬细胞来研究这些受体在介导巨噬细胞对分枝杆菌感染的反应中的意义。我们确定，在感染鸟分枝杆菌或耻垢分枝杆菌的巨噬细胞中，丝裂原活化蛋白激酶（MAPK）活化和肿瘤坏死因子-α（TNF-α）产生依赖于髓样分化因子88（MyD 88）和TLR 2，而不是TLR 4、MR或CR 3。有趣的是，TLR 2介导的TNF-α的产生需要β-葡聚糖受体dectin-1的巨噬细胞感染的耻垢分枝杆菌。在用牛分枝杆菌卡介苗（BCG）、草分枝杆菌、鸟分枝杆菌2151-粗糙和结核分枝杆菌H37 Ra感染的巨噬细胞中观察到TNF-α产生中对dectin-1的类似需求。毒力M avium 724和M tuberculosis H37 Rv的TNF-α的有限产生不依赖于dectin-1。此外，dectin-1促进白细胞介素-6（IL-6），RANTES（调节激活，正常T表达和分泌），和粒细胞集落刺激因子（G-CSF）的分枝杆菌感染的巨噬细胞的生产。这些是第一个结果，以建立一个显着的作用dectin-1，在TLR 2的合作，激活巨噬细胞的促炎反应，分枝杆菌感染。
Pattern recognition receptors (PRRs) play an essential role in a macrophage's response to mycobacterial infections. However, how these receptors work in concert to promote this macrophage response remains unclear. In this study, we used bone marrow-derived macrophages isolated from mannose receptor (MR), complement receptor 3 (CR3), MyD88, Toll-like receptor 4 (TLR4), and TLR2 knockout mice to examine the significance of these receptors in mediating a macrophage's response to a mycobacterial infection. We determined that mitogen-activated protein kinase (MAPK) activation and tumor necrosis factor-alpha (TNF-alpha) production in macrophage infected with Mycobacterium avium, or M smegmatis is dependent on myeloid differentiation factor 88 (MyD88) and TLR2 but not TLR4, MR, or CR3. Interestingly, the TLR2-mediated production of TNF-alpha by macrophages infected with M smegmatis required the P-glucan receptor dectin-1. A similar requirement for dectin-1 in TNF-a production was observed for macrophages infected with M bovis Bacillus Calmette-Guerin (BCG), M phlei, M avium 2151-rough, and M tuberculosis H37Ra. The limited production of TNF-alpha by virulent M avium 724 and M tuberculosis H37Rv was not dependent on dectin-1. Furthermore, dectin-1 facilitated interleukin-6 (IL-6), RANTES (regulated on activation, normal T expressed and secreted), and granulocyte colony-stimulating factor (G-CSF) production by mycobacteria-infected macrophages. These are the first results to establish a significant role for dectin-1, in cooperation with TLR2, to activate a macrophage's proinflammatory response to a mycobacterial infection.