Salmonella typhimurium infection in nonobese diabetic mice generates immunomodulatory dendritic cells able to prevent type 1 diabetes.
Infection, commencing across a wide age range, with a live, attenuated strain of Salmonella typhimurium, will halt the development of type 1 diabetes in the NOD mouse. The protective mechanism appears to involve the regulation of autoreactive T cells in a manner associated with long lasting changes in the innate immune compartment of these mice. We show in this study that autoreactive T cell priming and trafficking are altered in mice that have been infected previously by S. typhimurium. These changes are associated with sustained alterations in patterns of chemokine expression. We find that small numbers of dendritic cells from mice that have been previously infected with, but cleared all trace of a S. typhimurium infection are able to prevent the development of diabetes in the highly synchronized and aggressive cyclophosphamide-induced model. The effects we observe on autoreactive T cell trafficking are recapitulated by the immunomodulatory dendritic cell transfers in the cyclophosphamide model.
Raine
Tim
T
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom.
Zaccone
Paola
P
Mastroeni
Pietro
P
Cooke
Anne
A
D000818:Animals; D002478:Cells, Cultured; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC