TY - JOUR A1 - Wallaschek, Nina A1 - Reuter, Saskia A1 - Silkenat, Sabrina A1 - Wolf, Katharina A1 - Niklas, Carolin A1 - Özge, Kayisoglu A1 - Aguilar, Carmen A1 - Wiegering, Armin A1 - Germer, Christoph-Thomas A1 - Kircher, Stefan A1 - Rosenwald, Andreas A1 - Shannon-Lowe, Claire A1 - Bartfeld, Sina T1 - Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids JF - PLoS Pathogens N2 - Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection. KW - Organoids KW - ephitelial cells KW - gastrointestinal infections KW - cancers and neoplasms KW - Epstein-Barr virus KW - flow cytometry KW - epithelium Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259206 VL - 17 IS - 2 ER - TY - JOUR A1 - Rogoll, Dorothee A1 - Schauber, Jürgen A1 - Mheta, Koy K. A1 - Stich, August A1 - Scheppach, Wolfgang T1 - Differential Cathelicidin Expression in Duodenal and Gastric Biopsies from Tanzanian and German Patients JF - PLoS One N2 - Background Epithelial surfaces such as the gastrointestinal mucosa depend on expression of antimicrobial peptides like cathelicidin for immune defence against pathogens. The mechanisms behind mucosal cathelicidin regulation are incompletely understood. Methods Cathelicidin expression was analysed in duodenal, antral and corpus/fundic mucosal biopsies from African and German patients. Additionally, cathelicidin expression was correlated with Helicobacter pylori (HP) infection and the inflammatory status of the mucosa. Results High cathelicidin transcript abundance was detected in duodenal biopsies from African subjects. On the contrary, cathelicidin mRNA expression was either undetectable or very low in tissue specimens from German patients. Also, in the antrum and corpus/fundus regions of the stomach significantly higher cathelicidin transcript levels were measured in Tanzanian compared to German patients. In gastric biopsies from African patients cathelicidin expression was increased in HP positive compared to HP negative subjects. Additionally, the inflammatory status measured by IL-8 expression correlated well with the HP infection status. Conclusions A higher duodenal and gastric cathelicidin expression in African (compared with European) individuals may be due to upregulation by antigenic stimulation and may confer a higher resistance against enteric infections. KW - messenger RNA KW - german people KW - gastrointestinal tract KW - gastrointestinal infections KW - africans KW - antimicrobials KW - biopsy KW - helicobacter pylori infection Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137970 VL - 6 IS - 7 ER -