Plasticity of epithelial cell cytokine responses to commensal and pathogenic species

Background :It is well established that epithelial cells serve a sensory function and participate in the innate immune response to bacterial challenge. However, the epithelial response to commensal or probiotic bacteria is less well defined. Aims : To compare the temporal transcriptional responses of intestinal epithelial cells to commensal and pathogenic bacteria. Methods : The gene expression profiles of the human colorectal epithelial cell line HT29 was assessed at T0 and after bacterial stimulation at T1/2, T2, T6, T11 and T24 hours using cytokine gene expression array analysis (n=847 genes). The commensal strains used were Lactobacillus salivarius and Bifidobacterium infantis while the pathogenic strain was Salmonella typhimurium. Selected changes in gene expression were confirmed by RT-PCR. Results : The modulation of the gene expression profiles in HT29 cells as a consequence of bacterial stimulation were grouped into early (< 6 hours co-incubation) and late (> 11 hours co-incubation) transcriptional responses. The number of genes induced following incubation with each bacterial strain is illustrated in the figure. The early response to the lactobacillus and bifidobacterium strain were also observed in response to salmonella challenge. These gene changes seem to be part of the core epithelial response to bacterial stimulation. However a significantly increased variety of genes was expressed in response to salmonella challenge. In contrast, the late transcriptional responses differed amongst lactobacilli, bifidobacteria and salmonella. IL-8, Grobeta & Cox-2 gene expression were quantified using RT-PCR analysis, which confirmed the results obtained with gene array analysis. Conclusions : Shared core responses (eg. chemokines and cox-2 induction) and bacteria-specific responses ensure that sensory function of epithelial cells is coupled not only with a discriminatory response to pathogens vs commensals, but also appears to be commensal strain-specific..