The Scavenger Receptor SREC-I Cooperates with Toll-Like Receptors to Trigger Inflammatory Innate Immune Responses.
The Scavenger Receptor SREC-I Cooperates with Toll-Like Receptors to Trigger Inflammatory Innate Immune Responses.
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DOI：
10.3389/fimmu.2016.00226
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发表时间：
2016
影响因子：
7.3
通讯作者：
Calderwood SK
中科院分区：
文献类型：
--
作者：
Murshid A;Borges TJ;Lang BJ;Calderwood SK
内皮细胞-I 表达的清道夫受体 (SREC-I) 是免疫细胞表达的 F 类清道夫受体，在 CD8+- 和 CD4+ 介导的 T 细胞免疫中发挥重要作用。该受体还可以调节 Toll 样受体 (TLR) 的功能，TLR 在先天免疫中发挥重要作用。早些时候，人们发现人类单核细胞/巨噬细胞 THP1 细胞和小鼠骨髓来源的巨噬细胞对聚肌苷-聚胞苷酸 (poly I:C, PIC) 和 CpG（未甲基化）DNA 的反应增强，并且过度表达的 SREC-I 会增强炎症细胞因子的产生。我们的数据还表明，细胞内/内吞的 TLR3 和 TLR9 在各自配体存在的情况下可以直接与 SREC-I 相互作用。我们还观察到内化配体与 TLR3/TLR9 一起共定位于过表达这些受体的巨噬细胞和 THP-1 细胞的内体中。在没有这些配体的情况下，SREC-I 和内吞 TLR 之间没有可检测到的共定位。早些时候，研究表明，SREC-I 通过 NF-κB、IRF3 和 MAP 激酶途径触发信号传导，导致细胞因子基因转录，从而刺激双链 RNA/CpGDNA 介导的 TLR3/TLR9 激活先天免疫反应。我们还确定 SREC-I 可以与质膜 TLR 相关，例如 TLR2 和 TLR4。我们证明，SREC-I-TLR4 从脂质微域发出更有效的信号，其中脂多糖（LPS）可以与 SREC-I-TLR4 复合物结合。我们还证明，SREC-I 是 LPS 的替代受体，能够内化复合物，也是内吞 TLR 配体的替代受体。这种结合激活了 THP1 细胞和巨噬细胞中内吞 TLR 介导的下游细胞因子的产生。最后，SREC-I 还可以与 TLR2 形成复合物，并在细菌、病毒和真菌配体存在的情况下诱导细胞因子的释放。
Scavenger receptor expressed by endothelial cell-I (SREC-I) is a class F scavenger receptor expressed by immune cells with a significant role in CD8+- and CD4+-mediated T cell immunity. This receptor can also modulate the function of toll-like receptors (TLRs), which play essential roles in innate immunity. Earlier, it was found that human monocyte/macrophage THP1 cells and bone marrow-derived macrophages from mice exhibited increased responses to polyinosine–polycytidylic acid (poly I:C, PIC) and CpG (unmethylated) DNA and enhanced production of inflammatory cytokines with overexpressed SREC-I. Our data also showed that intracellular/endocytic TLR3 and TLR9 could directly interact with SREC-I in the presence of their respective ligands. We also observed that the internalized ligand along with TLR3/TLR9 colocalized in the endosome in macrophages and THP-1 cells overexpressing these receptors. In the absence of these ligands, there was no detectable colocalization between the SREC-I and endocytic TLRs. Earlier, it was shown that SREC-I stimulated double-stranded RNA/CpGDNA-mediated TLR3/TLR9 activation of the innate immune response by triggering signaling through the NF-κB, IRF3, and MAP kinase pathways leading to transcription of cytokine genes. We also established that SREC-I can associate with plasma membrane TLRs, such as TLR2 and TLR4. We demonstrated that SREC-I–TLR4 signals more efficiently from lipid microdomain in which lipopolysaccharide (LPS) can associate with SREC-I–TLR4 complex. We also proved that SREC-I is an alternate receptor for LPS capable of internalizing the complex and for endocytic TLR ligands as well. This binding activated endocytic TLR-mediated downstream cytokine production in THP1 cells and macrophages. Finally, SREC-I could also form complexes with TLR2 and induce the release of cytokines in the presence of bacterial, viral, and fungal ligands.