UCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA.
Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA 90095, USA.
Cell Stem Cell. 2020 Dec 3;27(6):869-875.e4. doi: 10.1016/j.stem.2020.11.010. Epub 2020 Nov 17.
Current smoking is associated with increased risk of severe COVID-19, but it is not clear how cigarette smoke (CS) exposure affects SARS-CoV-2 airway cell infection. We directly exposed air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term CS and then infected them with SARS-CoV-2. We found an increase in the number of infected airway cells after CS exposure with a lack of ABSC proliferation. Single-cell profiling of the cultures showed that the normal interferon response was reduced after CS exposure with infection. Treatment of CS-exposed ALI cultures with interferon β-1 abrogated the viral infection, suggesting one potential mechanism for more severe viral infection. Our data show that acute CS exposure allows for more severe airway epithelial disease from SARS-CoV-2 by reducing the innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to CS.
目前的研究表明，吸烟会增加感染严重 COVID-19 的风险，但目前尚不清楚香烟烟雾（CS）暴露如何影响 SARS-CoV-2 对气道细胞的感染。我们将源自人非吸烟气道基底干细胞（ABSC）的原代细胞的气液交界面（ALI）培养物直接暴露于短期 CS 中，然后用 SARS-CoV-2 感染它们。我们发现 CS 暴露后感染的气道细胞数量增加，而 ABSC 增殖缺乏。对培养物的单细胞分析显示，CS 暴露后干扰素反应正常减少，感染后进一步降低。用干扰素β-1 处理 CS 暴露的 ALI 培养物可阻断病毒感染，提示更严重病毒感染的一种潜在机制。我们的数据表明，急性 CS 暴露通过降低先天免疫反应和 ABSC 增殖，使 SARS-CoV-2 引起更严重的气道上皮疾病，并可能对接触 CS 的人群中的疾病传播和严重程度产生影响。
