title: Heligmosomoides polygyrus bakeri induces tolerogenic dendritic cells that block colitis and prevent antigen-specific gut T cell responses.
abstract: Immunological diseases such as inflammatory bowel disease (IBD) are infrequent in less developed countries, possibly because helminths provide protection by modulating host immunity. In IBD murine models, the helminth Heligmosomoides polygyrus bakeri prevents colitis. It was determined whether H. polygyrus bakeri mediated IBD protection by altering dendritic cell (DC) function. We used a Rag IBD model where animals were reconstituted with IL10⁻/⁻ T cells, making them susceptible to IBD and with OVA Ag-responsive OT2 T cells, allowing study of a gut antigenic response. Intestinal DC from H. polygyrus bakeri-infected Rag mice added to lamina propria mononuclear cells (LPMC) isolated from colitic animals blocked OVA IFN-γ/IL-17 responses in vitro through direct contact with the inflammatory LPMC. DC from uninfected Rag mice displayed no regulatory activity. Transfer of DC from H. polygyrus bakeri-infected mice into Rag mice reconstituted with IL10⁻/⁻ T cells protected animals from IBD, and LPMC from these mice lost OVA responsiveness. After DC transfer, OT2 T cells populated the intestines normally. However, the OT2 T cells were rendered Ag nonresponsive through regulatory action of LPMC non-T cells. The process of regulation appeared to be regulatory T cell independent. Thus, H. polygyrus bakeri modulates intestinal DC function, rendering them tolerogenic. This appears to be an important mechanism through which H. polygyrus bakeri suppresses colitis. IFN-γ and IL-17 are colitogenic. The capacity of these DC to block a gut Ag-specific IFN-γ/IL-17 T cell response also is significant.
authors: Division of Gastroenterology-Hepatology, Department of Internal Medicine, Tufts Medical Center, Boston, MA 02111, USA.
authors: Arthur M
authors: AM
authors: Blum
authors: Long
authors: L
authors: Hang
authors: Tommy
authors: T
authors: Setiawan
authors: Joseph P
authors: JP
authors: Urban
authors: Korynn M
authors: KM
authors: Stoyanoff
authors: John
authors: J
authors: Leung
authors: Joel V
authors: JV
authors: Weinstock
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D004195:Disease Models, Animal; D004760:Enterocolitis / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007108:Immune Tolerance; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D016753:Interleukin-10 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009351:Nematospiroides dubius / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000469:parasitology / Q000473:pathology
chemical_list: D018984:Epitopes, T-Lymphocyte; C556062:IL10 protein, mouse; D016753:Interleukin-10