病毒,如SARS-CoV-2,使用呼吸道上皮细胞作为感染的切入点。在鼻腔内,嗅觉上皮(OE)对可能导致嗅觉功能障碍的感染特别敏感。在患有COVID-19的患者中,嗅觉缺陷被描述为一种独特的症状。这里,我们使用K18hACE2小鼠研究了感染7天后SARS-CoV-2感染和嗅觉系统(OS)中炎症的传播。在OE中,我们发现SARS-CoV-2选择性地靶向固有层的支持/支持细胞(SC)和巨噬细胞。在大脑中,SARS-CoV-2感染嗅球(OB)中的一些小胶质细胞,和OB中投射神经元的广泛感染,梨状皮质(PC),和管状纹状体(TuS)。炎症,由数量升高和形态激活的IBA1+细胞(单核细胞/巨噬细胞谱系)表示,在OE隔膜中优先增加,虽然它均匀分布在OB的各层中,PC,和TUS。髓鞘OS轴突束,外侧嗅道,和前连合,表现出降低的CNPase水平,表明髓鞘缺陷。总的来说,我们的工作支持以下假设:SARS-CoV-2在OE和中央感染SC和巨噬细胞,小胶质细胞和OS神经元亚群。在整个OS区域观察到的炎症和中央髓鞘缺陷可能是造成长期嗅觉缺陷的原因。重要性声明在COVID-19期间可能导致嗅觉丧失的嗅觉系统损害仍然存在争议。使用感染SARS-CoV-2的K18hACE2小鼠,我们显示了嗅觉上皮中的硬细胞和固有层巨噬细胞的感染,而不是嗅觉感觉神经元的感染。在大脑中,我们在嗅球(OB)中发现了投射神经元的广泛感染,梨状皮质,和管状纹状体,伴有小胶质细胞增生。在OB中观察到一些SARS-CoV-2感染的小胶质细胞。我们还发现了嗅束中髓磷脂完整性的改变。这些数据支持SARS-CoV-2进入大脑的非嗅觉进入途径的假设,以及嗅束中神经元传导性的受损。
Viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), use respiratory epithelial cells as an entry point for infection. Within the nasal cavity, the olfactory epithelium (OE) is particularly sensitive to infections which may lead to olfactory dysfunction. In patients suffering from coronavirus disease 2019, deficits in olfaction have been characterized as a distinctive symptom. Here, we used the K18hACE2 mice to study the spread of SARS-CoV-2 infection and inflammation in the olfactory system (OS) after 7 d of infection. In the OE, we found that SARS-CoV-2 selectively targeted the supporting/sustentacular cells (SCs) and macrophages from the lamina propria. In the brain, SARS-CoV-2 infected some microglial cells in the olfactory bulb (OB), and there was a widespread infection of projection neurons in the OB, piriform cortex (PC), and tubular striatum (TuS). Inflammation, indicated by both elevated numbers and morphologically activated IBA1+ cells (monocyte/macrophage lineages), was preferentially increased in the OE septum, while it was homogeneously distributed throughout the layers of the OB, PC, and TuS. Myelinated OS axonal tracts, the lateral olfactory tract, and the anterior commissure, exhibited decreased levels of 2\',3\'-cyclic-nucleotide 3\'-phosphodiesterase, indicative of myelin defects. Collectively, our work supports the hypothesis that SARS-CoV-2 infected SC and macrophages in the OE and, centrally, microglia and subpopulations of OS neurons. The observed inflammation throughout the OS areas and central myelin defects may account for the long-lasting olfactory deficit.