ABSTRACTIntestinal epithelial cells and antigen-presenting cells orchestrate mucosal innate immunity. This study investigated the role of bacterial DNA in modulating epithelial and bone marrow-derived antigen-presenting cells (BM-APCs) and subsequent T-lymphocyte responses. Murine MODE-K epithelial cells and BM-APCs were treated with DNA from eitherBifidobacterium breveorSalmonella entericaserovar Dublin directly and under coculture conditions with CD4+T cells. Apical stimulation of MODE-K cells withS. Dublin DNA enhanced secretion of cytokines from underlying BM-APCs and induced interleukin-17 (IL-17) and gamma interferon (IFN-γ) secretion from CD4+T cells. Bacterial DNA isolated from either strain induced maturation and increased cytokine secretion from BM-APCs. Conditioned medium fromS. Dublin-treated MODE-K cells elicited an increase in cytokine secretion similar to that seen forS. Dublin DNA. Treatment of conditioned medium from MODE-K cells with RNase and protease prevented theS. Dublin-induced increased cytokine secretion. Oral feeding of mice withB. breveDNA resulted in enhanced levels of colonic IL-10 and transforming growth factor β (TGFβ) compared with what was seen for mice treated withS. Dublin DNA. In contrast, feeding mice withS. Dublin DNA increased levels of colonic IL-17 and IL-12p70. T cells fromS. Dublin DNA-treated mice secreted high levels of IL-12 and IFN-γ compared to controls andB. breveDNA-treated mice. These results demonstrate that intestinal epithelial cells are able to modulate subsequent antigen-presenting and T-cell responses to bacterial DNA with pathogenic but not commensal bacterial DNA inducing effector CD4+T lymphocytes.
The Hemorrhagic Coli Pilus (HCP) of Escherichia coli O157:H7 Is an Inducer of Proinflammatory Cytokine Secretion in Intestinal Epithelial Cells