title: Intestinal epithelial cells modulate antigen-presenting cell responses to bacterial DNA.
abstract: Intestinal 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 either Bifidobacterium breve or Salmonella enterica serovar Dublin directly and under coculture conditions with CD4(+) T cells. Apical stimulation of MODE-K cells with S. 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 from S. Dublin-treated MODE-K cells elicited an increase in cytokine secretion similar to that seen for S. Dublin DNA. Treatment of conditioned medium from MODE-K cells with RNase and protease prevented the S. Dublin-induced increased cytokine secretion. Oral feeding of mice with B. breve DNA resulted in enhanced levels of colonic IL-10 and transforming growth factor β (TGFβ) compared with what was seen for mice treated with S. Dublin DNA. In contrast, feeding mice with S. Dublin DNA increased levels of colonic IL-17 and IL-12p70. T cells from S. Dublin DNA-treated mice secreted high levels of IL-12 and IFN-γ compared to controls and B. breve DNA-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.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Campeau
authors.forename: S Y
authors.initials: SY
authors.lastname: Salim
authors.forename: E J
authors.initials: EJ
authors.lastname: Albert
authors.forename: N
authors.initials: N
authors.lastname: Hotte
authors.forename: K L
authors.initials: KL
authors.lastname: Madsen
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D001644:Bifidobacterium / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D002460:Cell Line; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000276:immunology*; D004847:Epithelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D007249:Inflammation / Q000382:microbiology; D007413:Intestinal Mucosa / Q000166:cytology*; D051379:Mice; D012481:Salmonella Infections, Animal / Q000382:microbiology; D019779:Salmonella enterica / Q000235:genetics* / Q000276:immunology
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D004269:DNA, Bacterial