Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12
Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12
复制标题
DOI：
10.1038/ni1204
复制
发表时间：
2005-06-01
影响因子：
30.5
通讯作者：
Lanier, LL
中科院分区：
文献类型：
--
作者：
Hamerman, JA;Tchao, NK;Lanier, LL
DAP 12是一种信号转导衔接子，含有与骨髓细胞和自然杀伤细胞上的受体配对的基于免疫受体酪氨酸的激活基序（ITAM）。我们在这里检查缺乏DAP 12的小鼠通过Toll样受体（TLR）对刺激的反应。出乎意料的是，DAP 12缺陷型巨噬细胞产生更高浓度的炎性细胞因子，以响应各种致病性刺激。此外，巨噬细胞缺乏脾酪氨酸激酶（Syk），其信号下游的DAP 12，表现出相同的表型的DAP 12-缺陷的巨噬细胞。DAP 12缺陷小鼠更容易发生内毒素休克，并且对细胞内细菌单核细胞增生李斯特菌的感染具有增强的抵抗力。这些数据表明，一个或多个DAP 12配对受体通过TLR负调控信号传导。
DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced higher concentrations of inflammatory cytokines in response to a variety of pathogenic stimuli. Additionally, macrophages deficient in spleen tyrosine kinase (Syk), which signals downstream of DAP12, showed a phenotype identical to that of DAP12-deficient macrophages. DAP12-deficient mice were more susceptible to endotoxic shock and had enhanced resistance to infection by the intracellular bacterium Listeria monocytogenes. These data suggest that one or more DAP12-pairing receptors negatively regulate signaling through TLRs.