摘要
Bearing in mind that mast cell contribution to viral clearance is still not fully understood, in this study, we evaluated the effect of Toll-like receptor (TLR)7 viral single-stranded ribonucleic acid (ssRNA) mimic ligand, namely resiquimod (R)848, on mast cell phenotype and activity. We demonstrated that rat peritoneal mast cells exhibit surface and intracellular expression of ssRNA-specific TLR7 molecule, and that mimic ligand switches the self-expression of this receptor. We also detected other proteins associated with the cellular antiviral response: interferon-alpha receptor 1 (IFNAR1), interferon-gamma receptor 1 (IFNGR1), and major histocompatibility complex I (MHC I). Moreover, we showed that R848 caused the decrease of all molecule’s expression after prolonged incubation. Interestingly, we found that R848 induced the increase of high-affinity IgE receptor (FcεRI) expression. Finally, we documented that TLR7 ligand-stimulated mast cells synthesize/release interferon (IFN)-α and -β, tumor necrosis factor (TNF), and chemokines CCL3, CXCL8, as well as pro-inflammatory lipid mediators. Our findings confirm that mast cells may respond to TLR7 ligand by altering their phenotype and synthesizing mediators and could serve as active participants in the antiviral immune response.
摘要译文
考虑到肥大细胞对病毒清除的贡献尚不完全清楚，在这项研究中，我们评估了Toll样受体（TLR）7病毒单链核糖核酸（ssRNA）模拟配体即雷西莫德（R）的作用848，关于肥大细胞的表型和活性。我们证明了大鼠腹膜肥大细胞表现出ssRNA特异性的TLR7分子的表面和细胞内表达，并且模仿配体改变了该受体的自我表达。我们还检测了其他与细胞抗病毒反应有关的蛋白质：干扰素-α受体1（IFNAR1），干扰素-γ受体1（IFNGR1）和主要组织相容性复合体I（MHC I）。此外，我们证明了R848长时间孵育后会导致所有分子的表达下降。有趣的是，我们发现R848诱导了高亲和力IgE受体（FcεRI）表达的增加。最后，我们证明了受TLR7配体刺激的肥大细胞合成/释放干扰素（IFN）-α和-β，肿瘤坏死因子（TNF）和趋化因子CCL3，CXCL8以及促炎性脂质介体。我们的发现证实，肥大细胞可以通过改变其表型和合成介体来响应TLR7配体，并且可以作为抗病毒免疫反应的积极参与者。
JustynaAgier;EwaBrzezińska-Błaszczyk;PiotrWitczak;ElżbietaKozłowska;PaulinaŻelechowska;. The impact of TLR7 agonist R848 treatment on mast cell phenotype and activity - ScienceDirect[J]. Cellular Immunology, 2021,359