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Different cell models have been used to study EPEC infection, but a direct comparison of infection of cell lines and primary cells is lacking. In this study, we compare EPEC infection in primary epithelial cells with HeLa cells. Jejunal organoid\u2010derived cells contain differentiated intestinal epithelial cells and form a tight monolayer. Upon infection, they retain integrity over longer time periods than HeLa cells. Attachment of EPEC to host cells and innate immune response is strongly delayed in organoid\u2010derived monolayers. These results indicate that host cell factors determine the outcome of infection. 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