Rotavirus infection of cultured intestinal epithelial cells induces secretion of CXC and GC chemokines

Background & Aims: Rotaviruses are the major cause of pediatric gastroenteritis worldwide. The target cell of rotavirus infection is the mature enterocyte of the small intestine. Recently, intestinal epithelial cells have been shown to produce chemoattractant mediators in response to cytokine stimulation and bacterial infection, suggesting a potentially important role of epithelial cells in initiating immune responses. In this study, the production of chemokines by cultured intestinal epithelial cells after rotavirus infection was investigated. Methods: Two human intestinal epithelial cell lines (HT29 and Caco-2) were infected with sucrose-purified rotavirus (strain SA114F) and assayed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay for chemokine expression. Virus-like particles and inactivated rotavirus were used to test the importance of viral attachment and replication. Results: Increased messenger RNA expression and secretion of immunoreactive interleukin 8, growth-related peptide alpha, and RANTES (regulated upon activation, normal T cell expressed and secreted) were detected in rotavirus-infected cells. Chemokine production was time and dose dependent and required viral replication. Conclusions: Rotavirus infection induces the expression of a subset of chemokines in intestinal epithelial cells. These data support the hypothesis that chemokine secretion by enterocytes may play a role in the initiation and modulation of the immune response to rotavirus infection.