Endosomal toll-like receptors play a key role in activation of primary human monocytes by cowpea mosaic virus
Endosomal toll-like receptors play a key role in activation of primary human monocytes by cowpea mosaic virus
复制标题
DOI：
10.1111/imm.13135
复制
发表时间：
2019-11-15
期刊：
影响因子：
6.4
通讯作者：
Sieg, Scott F.
中科院分区：
文献类型：
--
作者：
Albakri, Marwah M.;Veliz, Frank A.;Sieg, Scott F.
这种植物病毒——豇豆花叶病毒（CPMV）在直接施用到实体瘤中后已表现出诱导抗肿瘤免疫反应的显着能力。解释这些效应的分子途径以及 CPMV 激活人类细胞的能力尚未明确。在这里，我们检查了 CPMV 颗粒激活人类单核细胞、树突状细胞 (DC) 和巨噬细胞的能力。外周血单核细胞培养物中的单核细胞和纯化的 CD14+ 单核细胞在体外很容易被 CPMV 激活，从而诱导 HLA-DR、CD86、PD-L1、IL-15R 和 CXCL10 表达。与 CPMV 孵育后，单核细胞将趋化因子、CXCL10、MIP-1 α 和 MIP-1 β 释放到细胞培养物上清液中。 DC 子集（pDC 和 mDC）和单核细胞来源的巨噬细胞也显示出与 CPMV 孵育后激活的证据。脾酪氨酸激酶 (SYK) 抑制剂、内吞作用或内吞酸化会损害 CPMV 激活单核细胞的能力。此外，单核细胞的 CPMV 激活被 TLR7/8 拮抗剂部分阻断。这些数据表明，CPMV 以依赖于 SYK 信号传导、内体酸化的方式激活人类单核细胞，并且 TLR7/8 识别发挥了重要作用。
The plant virus, cowpea mosaic virus (CPMV), has demonstrated a remarkable capacity to induce anti-tumour immune responses following direct administration into solid tumours. The molecular pathways that account for these effects and the capacity of CPMV to activate human cells are not well defined. Here, we examine the ability of CPMV particles to activate human monocytes, dendritic cells (DCs) and macrophages. Monocytes in peripheral blood mononuclear cell cultures and purified CD14+ monocytes were readily activated by CPMV in vitro, leading to induction of HLA-DR, CD86, PD-L1, IL-15R and CXCL10 expression. Monocytes released chemokines, CXCL10, MIP-1 alpha and MIP-1 beta into cell culture supernatants after incubation with CPMV. DC subsets (pDC and mDC) and monocyte-derived macrophages also demonstrated evidence of activation after incubation with CPMV. Inhibitors of spleen tyrosine kinase (SYK), endocytosis or endocytic acidification impaired the capacity of CPMV to activate monocytes. Furthermore, CPMV activation of monocytes was partially blocked by a TLR7/8 antagonist. These data demonstrate that CPMV activates human monocytes in a manner dependent on SYK signalling, endosomal acidification and with an important contribution from TLR7/8 recognition.