Intestinal Protein Characterisation of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2 in Inflammatory Bowel Disease (IBD) and Fatal COVID-19 Infection.
Intestinal Protein Characterisation of SARS-CoV-2 Entry Molecules ACE2 and TMPRSS2 in Inflammatory Bowel Disease (IBD) and Fatal COVID-19 Infection.
复制标题
DOI：
10.1007/s10753-021-01567-z
复制
发表时间：
2022-04
期刊：
影响因子：
5.1
通讯作者：
Ho GT
中科院分区：
文献类型：
--
作者：
McAllister MJ;Kirkwood K;Chuah SC;Thompson EJ;Cartwright JA;Russell CD;Dorward DA;Lucas CD;Ho GT
冠状病毒SARS-CoV-2主要由于肺部的免疫病理学而导致发病率和死亡率。最近的数据表明，多系统参与广泛的病毒嗜性。在这里，我们提出了一个详细的肠道蛋白质特征的SARS-Cov-2进入分子ACE 2和TMPRSS 2在炎症性肠病患者（[IBD];溃疡性结肠炎[UC]和克罗恩病[CD]）与年龄和性别匹配的非IBD对照，以及致命的COVID-19感染。在我们的数据集中，ACE 2和TMPRSS 2显示回肠中的膜肠上皮细胞染色（由于存在刷状缘/微绒毛），与结肠中的细胞质模式相反。我们还显示了高ACE 2/低TMPRSS 2表达模式在回肠中与结肠中的相反趋势。在UC中，结肠ACE 2和TMPRSS 2本质上是细胞质的，与非IBD对照相比具有显著更高的ACE 2染色强度。在炎症和未受影响的IBD粘膜中，回肠和结肠肠上皮细胞ACE 2和TMPRSS 2表达在炎症的组织学存在下没有改变。我们观察到固有层内表达ACE 2和TMPRSS 2的免疫细胞，与非IBD对照相比，IBD中的频率更高。这些被鉴定为具有多发性骨髓瘤癌基因1/干扰素调节因子4（MUM 1/IRF 4）表达的浆细胞。我们进一步分析了6例致死性COVID-19病例的肠道组织学，结肠和回肠ACE 2/TMRPSS 2染色无差异（与非IBD对照相比），并鉴定了ACE 2+固有层浆细胞。有趣的是，在该COVID-19队列中，尽管已知肠细胞内存在病毒嗜性的证据，但没有组织学证据显示肠道炎症。我们的数据为进入分子ACE 2和TMPRSS 2的组织表达提供了证据，包括与浆细胞的紧密结合-两者都指向肠道在SARS-CoV-2感染的前期免疫反应中的作用。在线版本包含补充材料，可通过10.1007/s10753-021-01567-z获得。
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. The online version contains supplementary material available at 10.1007/s10753-021-01567-z.
登录
查看更多内容
DOI：
10.1093/ecco-jcc/jjaa185
发表时间：
2021-03-05
期刊：
Journal of Crohn's & colitis
影响因子：
--
作者：
Verstockt B;Verstockt S;Abdu Rahiman S;Ke BJ;Arnauts K;Cleynen I;Sabino J;Ferrante M;Matteoli G;Vermeire S
通讯作者：
Vermeire S
影响因子：
64.8
作者：
Gaebler C;Wang Z;Lorenzi JCC;Muecksch F;Finkin S;Tokuyama M;Cho A;Jankovic M;Schaefer-Babajew D;Oliveira TY;Cipolla M;Viant C;Barnes CO;Bram Y;Breton G;Hägglöf T;Mendoza P;Hurley A;Turroja M;Gordon K;Millard KG;Ramos V;Schmidt F;Weisblum Y;Jha D;Tankelevich M;Martinez-Delgado G;Yee J;Patel R;Dizon J;Unson-O'Brien C;Shimeliovich I;Robbiani DF;Zhao Z;Gazumyan A;Schwartz RE;Hatziioannou T;Bjorkman PJ;Mehandru S;Bieniasz PD;Caskey M;Nussenzweig MC
通讯作者：
Nussenzweig MC
IGA主导对SARS-COV-2的早期中和抗体反应。
影响因子：
17.1
作者：
Sterlin D;Mathian A;Miyara M;Mohr A;Anna F;Claër L;Quentric P;Fadlallah J;Devilliers H;Ghillani P;Gunn C;Hockett R;Mudumba S;Guihot A;Luyt CE;Mayaux J;Beurton A;Fourati S;Bruel T;Schwartz O;Lacorte JM;Yssel H;Parizot C;Dorgham K;Charneau P;Amoura Z;Gorochov G
通讯作者：
Gorochov G
影响因子：
29.4
作者：
通讯作者：
--
影响因子：
9.9
作者：
Hikmet, Feria;Mear, Loren;Lindskog, Cecilia
通讯作者：
Lindskog, Cecilia