Adoptive transfer of helminth antigen-pulsed dendritic cells protects against the development of experimental colitis in mice.
Infection with helminth parasites and treatment with worm extracts can suppress inflammatory disease, including colitis. Postulating that dendritic cells (DCs) participated in the suppression of inflammation and seeking to move beyond the use of helminths per se, we tested the ability of Hymenolepis diminuta antigen-pulsed DCs to suppress colitis as a novel cell-based immunotherapy. Bone marrow derived DCs pulsed with H. diminuta antigen (HD-DCs), or PBS-, BSA-, or LPS-DCs as controls, were transferred into wild-type (WT), interleukin-10 (IL-10) knock-out (KO), and RAG-1 KO mice, and the impact on dinitrobenzene sulphonic acid (DNBS)-induced colitis and splenic cytokine production assessed 72 h later. Mice receiving HD-DCs were significantly protected from DNBS-induced colitis and of the experimental groups only these mice displayed increased Th2 cytokines and IL-10 production. Adoptive transfer of HD-DCs protected neither RAG-1 nor IL-10 KO mice from DNBS-colitis. Furthermore, the transfer of CD4(+) splenocytes from recipients of HD-DCs protected naïve mice against DNBS-colitis, in an IL-10 dependent manner. Thus, HD-DCs are a novel anti-colitic immunotherapy that can educate anti-colitic CD4(+) T cells: mechanistically, the anti-colitic effect of HD-DCs requires that the host has an adaptive immune response and the ability to mobilize IL-10.
Department of Physiology and Pharmacology, Gastrointestinal Research Group and Inflammation Research Network, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Chelsea E
CE
Matisz
Department of Physiology and Pharmacology, Gastrointestinal Research Group and Inflammation Research Network, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Gabriella
G
Leung
Department of Physiology and Pharmacology, Gastrointestinal Research Group and Inflammation Research Network, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Jose Luis
JL
Reyes
Department of Physiology and Pharmacology, Gastrointestinal Research Group and Inflammation Research Network, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Arthur
A
Wang
Department of Physiology and Pharmacology, Gastrointestinal Research Group and Inflammation Research Network, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Keith A
KA
Sharkey
Department of Physiology and Pharmacology, Gastrointestinal Research Group and Inflammation Research Network, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Derek M
DM
McKay
D019264:Adoptive Transfer; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D003092:Colitis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D048190:Hymenolepis diminuta / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout
D000947:Antigens, Helminth
Colitis; Dendritic cells; Helminth antigen; Hymenolepis diminuta antigen; IL-10