Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK.
Gastroenterology and Pathology Department, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK.
Inflammation. 2022 Apr;45(2):567-572. doi: 10.1007/s10753-021-01567-z. Epub 2021 Oct 25.
The coronavirus SARS-CoV-2 contributes to morbidity and mortality mainly as a result of immune-pathology in the lungs. Recent data has shown multi-system involvement with widespread viral tropism. Here we present a detailed intestinal protein characterisation of SARS-Cov-2 entry molecules ACE2 and TMPRSS2 in patients with inflammatory bowel disease ([IBD]; ulcerative colitis [UC] and Crohn's disease [CD]) with age- and sex-matched non-IBD controls, and in those with fatal COVID-19 infection. In our dataset, ACE2 and TMPRSS2 displayed a membrane enterocyte staining in the ileum (due to presence of brush border/microvilli) in contrast to a cytoplasmic pattern in the colon. We also showed a high ACE2/low TMPRSS2 expression pattern in the ileum with a reverse trend in the colon. In UC, colonic ACE2 and TMPRSS2 are cytoplasmic in nature, with significantly higher ACE2 staining intensity compared to non-IBD controls. In inflamed and unaffected IBD mucosa, ileal and colonic enterocyte ACE2 and TMPRSS2 expressions are not modified in the histologic presence of inflammation. We observed immune cells within the lamina propria that expressed ACE2 and TMPRSS2, at higher frequencies in IBD when compared to non-IBD controls. These were identified as plasma cells with multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) expression. We further analysed the gut histology of six fatal COVID-19 cases, with no difference in colonic and ileal ACE2/TMRPSS2 staining (compared to non-IBD controls) and identified ACE2 + lamina propria plasma cells. Of interest, in this COVID-19 cohort, there was no histologic evidence gut inflammation despite known evidence of viral tropism within the enterocytes. Our data provides evidence for tissue expression of entry molecules ACE2 and TMPRSS2 including a close apposition to plasma cells - both pointing towards a role of the gut in the antecedent immune response to SARS-CoV-2 infection.
冠状病毒 SARS-CoV-2 主要通过肺部的免疫病理学导致发病率和死亡率。最近的数据表明，病毒具有广泛的组织嗜性，涉及多系统。在这里，我们对患有炎症性肠病（IBD；溃疡性结肠炎 [UC] 和克罗恩病 [CD]）的患者以及患有致命 COVID-19 感染的患者的肠道 ACE2 和 TMPRSS2 进入分子进行了详细的肠道蛋白特征分析，这些患者与年龄和性别匹配的非 IBD 对照组进行了比较。在我们的数据集，ACE2 和 TMPRSS2 在回肠中显示出肠上皮细胞的膜染色（由于存在刷状缘/微绒毛），而在结肠中则呈现细胞质模式。我们还显示出回肠中 ACE2 高/TMPRSS2 低的表达模式，而在结肠中则呈现相反的趋势。在 UC 中，结肠 ACE2 和 TMPRSS2 本质上是细胞质的，与非 IBD 对照组相比，ACE2 染色强度显著更高。在炎症和非炎症 IBD 黏膜中，炎症存在时，回肠和结肠肠上皮细胞 ACE2 和 TMPRSS2 的表达没有改变。我们观察到固有层内有表达 ACE2 和 TMPRSS2 的免疫细胞，在 IBD 中比非 IBD 对照组更为常见。这些细胞被鉴定为浆细胞，具有多发性骨髓瘤癌基因 1/干扰素调节因子 4（MUM1/IRF4）表达。我们进一步分析了 6 例致命 COVID-19 病例的肠道组织学，发现结肠和回肠 ACE2/TMRPSS2 染色（与非 IBD 对照组相比）没有差异，并鉴定出 ACE2+固有层浆细胞。有趣的是，在 COVID-19 队列中，尽管已知肠上皮细胞内有病毒嗜性，但没有组织炎症的组织学证据。我们的数据提供了 ACE2 和 TMPRSS2 进入分子的组织表达证据，包括与浆细胞的紧密接近-这两者都指向肠道在 SARS-CoV-2 感染的先前免疫反应中的作用。
