Evidence of SARS-CoV2 Entry Protein ACE2 in the Human Nose and Olfactory Bulb
Evidence of SARS-CoV2 Entry Protein ACE2 in the Human Nose and Olfactory Bulb
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DOI：
10.1159/000513040
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发表时间：
2021-01-22
影响因子：
2.7
通讯作者：
Milazzo, Alfio
中科院分区：
文献类型：
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作者：
Klingenstein, Moritz;Klingenstein, Stefanie;Milazzo, Alfio
通常，由SARS-CoV2引起的COVID-19大流行疾病表现为轻微的呼吸道症状，如发烧、咳嗽，但也经常伴有嗅觉丧失和神经系统症状。病毒与细胞融合是由血管紧张素转换酶2 （ACE2）和跨膜丝氨酸蛋白酶2 （TMPRSS2）介导的，它们的器官表达模式决定了病毒的趋向性。临床表现表明病毒迅速传播到中枢神经系统，经常导致包括病毒性脑膜炎在内的严重症状。在这里，我们提供了ACE2和TMPRSS2蛋白在人死后鼻腔和嗅觉组织中的全面表达图谱。通过人鼻子的矢状面切片，辅以各自细胞类型的免疫标记，代表了不同的解剖定义区域，包括嗅上皮、鼻甲壳呼吸上皮和鼻窦，以及难以接近的人嗅球。ACE2可在鼻中隔、鼻甲壳和鼻窦的嗅上皮以及呼吸上皮中检测到。ACE2位于嗅觉上皮的支撑细胞和腺细胞以及呼吸上皮的基底细胞、腺细胞和上皮细胞中。有趣的是，ACE2在嗅上皮的成熟或未成熟嗅觉受体神经元和基底细胞中均不表达。同样，尽管嗅球呈阳性，但ACE2并不局限于嗅觉受体神经元。反之，TMPRSS2也可在嗅上皮的支撑细胞和腺细胞中检测到。我们的发现为ACE2和TMPRSS2在人鼻、嗅上皮和嗅球中的表达提供了基本的解剖学依据。因此，它们对未来旨在通过嗅觉途径阐明SARS-CoV2诱导的嗅觉缺失症状的研究具有重要意义。
Usually, pandemic COVID-19 disease, caused by SARS-CoV2, presents with mild respiratory symptoms such as fever, cough, but frequently also with anosmia and neurological symptoms. Virus-cell fusion is mediated by angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with their organ expression pattern determining viral tropism. Clinical presentation suggests rapid viral dissemination to the central nervous system leading frequently to severe symptoms including viral meningitis. Here, we provide a comprehensive expression landscape of ACE2 and TMPRSS2 proteins across human postmortem nasal and olfactory tissue. Sagittal sections through the human nose complemented with immunolabelling of respective cell types represent different anatomically defined regions including olfactory epithelium, respiratory epithelium of the nasal conchae and the paranasal sinuses along with the hardly accessible human olfactory bulb. ACE2 can be detected in the olfactory epithelium as well as in the respiratory epithelium of the nasal septum, the nasal conchae, and the paranasal sinuses. ACE2 is located in the sustentacular cells and in the glandular cells in the olfactory epithelium as well as in the basal cells, glandular cells, and epithelial cells of the respiratory epithelium. Intriguingly, ACE2 is not expressed in mature or immature olfactory receptor neurons and basal cells in the olfactory epithelium. Similarly, ACE2 is not localized in the olfactory receptor neurons albeit the olfactory bulb is positive. Vice versa, TMPRSS2 can also be detected in the sustentacular cells and the glandular cells of the olfactory epithelium. Our findings provide the basic anatomical evidence for the expression of ACE2 and TMPRSS2 in the human nose, olfactory epithelium, and olfactory bulb. Thus, they are substantial for future studies that aim to elucidate the symptom of SARS-CoV2 induced anosmia via the olfactory pathway.