Oxidant and Inflammation Biology Group, School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, 3083, Australia.
Department of Pharmacology, Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
Sci Rep. 2019 Feb 20;9(1):2366. doi: 10.1038/s41598-019-38864-5.
Toll-like receptor 7 (TLR7) is a pattern recognition receptor that recognizes viral RNA following endocytosis of the virus and initiates a powerful immune response characterized by Type I IFN production and pro-inflammatory cytokine production. Despite this immune response, the virus causes very significant pathology, which may be inflammation-dependent. In the present study, we examined the effect of intranasal delivery of the TLR7 agonist, imiquimod or its topical formulation Aldara, on the inflammation and pathogenesis caused by IAV infection. In mice, daily intranasal delivery of imiquimod prevented peak viral replication, bodyweight loss, airway and pulmonary inflammation, and lung neutrophils. Imiquimod treatment also resulted in a significant reduction in pro-inflammatory neutrophil chemotactic cytokines and prevented the increase in viral-induced lung dysfunction. Various antibody isotypes (IgG1, IgG2a, total IgG, IgE and IgM), which were increased in the BALF following influenza A virus infection, were further increased with imiquimod. While epicutaneous application of Aldara had a significant effect on body weight, it did not reduce neutrophil and eosinophil airway infiltration; indicating less effective drug delivery for this formulation. We concluded that intranasal imiquimod facilitates a more effective immune response, which can limit the pathology associated with influenza A virus infection.
Toll 样受体 7（TLR7）是一种模式识别受体，在病毒内化后识别病毒 RNA，并引发强大的免疫反应，其特征是产生 I 型干扰素和促炎细胞因子。尽管存在这种免疫反应，病毒仍会导致非常显著的病理学改变，这可能与炎症有关。在本研究中，我们研究了 TLR7 激动剂咪喹莫特或其局部制剂 Aldara 通过鼻腔内给药对 IAV 感染引起的炎症和发病机制的影响。在小鼠中，每天鼻腔内给予咪喹莫特可预防病毒复制峰值、体重减轻、气道和肺部炎症以及肺部中性粒细胞浸润。咪喹莫特治疗还显著降低了促炎中性粒细胞趋化细胞因子的水平，并防止了病毒诱导的肺功能障碍的增加。各种抗体同种型（IgG1、IgG2a、总 IgG、IgE 和 IgM）在流感 A 病毒感染后在 BALF 中增加，而咪喹莫特进一步增加了这些同种型。虽然 Aldara 的经皮应用对体重有显著影响，但它并没有减少中性粒细胞和嗜酸性粒细胞在气道中的浸润；这表明这种制剂的药物传递效果较差。我们得出结论，鼻腔内给予咪喹莫特可促进更有效的免疫反应，从而限制与流感 A 病毒感染相关的病理学改变。
