The effect of hypoxia on lipid raft organization and host‐pathogen interactions of intestinal epithelial cells (599.2)

Abstract

Oxygen stress, or hypoxia, occurs in tissues during an infection, mostly due to overconsumption of oxygen by pathogens and recruited immune cells. The aim of this study is to analyze the effect of hypoxia on host‐pathogen interactions and cellular responses of the intestinal epithelium upon infection. Therefore, Caco‐2 cells were grown under normoxia or hypoxia and were infected with Yersinia enterocolitica, a Gram‐negative bacterium that can cause severe gastrointestinal infections. Results show that invasion of Caco‐2 by Y. enterocolitica was significantly reduced in hypoxia‐treated cells while adherence remained unchanged. Since intestinal epithelial cells have been shown to regulate host‐pathogen interactions by means of detergent‐resistant membrane domains called lipid rafts, we further investigated the effect of hypoxia on lipid rafts. Interestingly, separation of lipid rafts isolated from Caco‐2 cells grown under hypoxia demonstrated that flotillin, a lipid rafts protein marker, exhibits a diffuse pattern in the rafts as well as non‐rafts fractions. By contrast, cells grown under normoxia revealed a clear flotillin distribution in the floating lipid rafts fractions. These results indicate that hypoxia leads to alterations of the intestinal epithelial cell membrane and suggests a protective effect of these membrane changes on host cells by hindering invasion of Y. enterocolitica.Grant Funding Source: Supported by DAAD and the German Research Council (DFG, grant number KO355214).