<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "The impact of the population context on virus infection, IFN response, and homeostatic immune signaling in mucosal epithelial cells"^^ . "Mucosal tissues act as a protective barrier in constant contact with microbiota. Epithelial cells on these surfaces must mount an effective immune response for protection from pathogens while minimizing adverse reactions to commensal microbiota. Each cell within these tissues has a specific population context, which is determined by the local cell density, cell-to-cell contacts, and relative location within the population. The aim of this thesis was to comprehensively elucidate how the cellular population context shapes viral infection and immune signaling pathways in epithelial tissues.\r\nTo this end, I employed human intestinal epithelial cells (IECs) as a model system for mucosal tissues. I developed a density-based approach and a micropatterning system to place cells in controlled microenvironments, which I combined with bio-molecular methods and microscopy/ sequencing-based high-content data bioinformatics analyses. My findings show that IECs embedded in a dense monolayer polarize, leading to a basolateral localization of the interferon (IFN) receptors. Hence, cells located in the center of a dense population did not induce antiviral protection upon apical IFN treatment due the receptor inaccessibility. Additionally, I discovered that the cellular microenvironment, especially the local cell density, controls homeostatic immune pathways. Confluent IEC expressed significant basal levels of IFNλ3 and downstream interferon stimulated genes, while sparse cells elicited no basal IFN-signaling. The basal type III IFN expression was induced by the cGAS-STING pathway after recognition of mitochondrial DNA. Importantly, the Hippo pathway emerged as the master regulator controlling homeostatic immune signaling, which senses the population context (e.g. cellular density and cell-to-cell contacts) to adjust cell behavior to its microenvironment. Finally, I established that the population context governs virus particle binding and active pathogen replication within a cell colony, leading to increased edge cell infection while center cells remained protected.\r\nThis thesis shows that the population context in vitro directly shapes homeostatic and antiviral processes in epithelial cells. Cells embedded in the intact monolayer elicit higher basal IFNλ3 expression and less virus infection, demonstrating that a physiological micro-environment supports the barrier function of mucosal surfaces. My work strongly suggests that the population context should be considered when planning experiments in vitro, and it also underlines the importance of studying the population context and its implications in vivo. \r\nIn light of the COVID-19 pandemic, I additionally characterized the role of type I and III IFNs signaling in controlling SARS-CoV-2 infection in the gut. My results indicate that type III IFNs are more efficient than type I IFNs in clearing SARS-CoV-2 infection in human intestinal epithelial cells. These findings further our understanding of host-pathogen interactions and could contribute to a development of improved treatment options."^^ . "2025" . . . . . . . "Camila"^^ . "Metz Zumaran"^^ . "Camila Metz Zumaran"^^ . . . . . . "The impact of the population context on virus infection, IFN response, and homeostatic immune signaling in mucosal epithelial cells (PDF)"^^ . . . "The impact of the population context on virus infection, IFN response, and homeostatic immune signaling in mucosal epithelial cells (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "The impact of the population context on virus infection, IFN response, and homeostatic immune signaling in mucosal epithelial cells (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "The impact of the population context on virus infection, IFN response, and homeostatic immune signaling in mucosal epithelial cells (Other)"^^ . . . . . . "preview.jpg"^^ . . . "The impact of the population context on virus infection, IFN response, and homeostatic immune signaling in mucosal epithelial cells (Other)"^^ . . . . . . "medium.jpg"^^ . . . "The impact of the population context on virus infection, IFN response, and homeostatic immune signaling in mucosal epithelial cells (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #34258 \n\nThe impact of the population context on virus infection, IFN response, and homeostatic immune signaling in mucosal epithelial cells\n\n" . "text/html" . . . "000 Allgemeines, Wissenschaft, Informatik"@de . "000 Generalities, Science"@en . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .