Salmonella typhimurium infection halts development of type 1 diabetes in NOD mice.
Infectious disease has been proposed as an environmental modifier of autoimmunity in both human populations and the NOD mouse. We found that infection of NOD mice with attenuated, but not killed, Salmonella typhimurium can reduce the incidence of type 1 diabetes (T1D), even if infection occurs after the development of a peri-islet pancreatic infiltrate. Functional diabetogenic effector T cells are still present, as demonstrated by the initiation of diabetes in NOD-scid recipients of transferred splenocytes. High levels of IFN-gamma are secreted by splenocytes of infected mice, but there is no evidence of involvement of IL-10 in the protective effect of the infection. Finally, prolonged changes in cell subsets are observed in infected mice involving invariant Valpha14Jalpha281 NuKappaTau and dendritic cells. These data reinforce the idea that prevention of T1D in the NOD mouse cannot be reduced to the simple Th1/Th2 paradigm and that different infections may involve different protective mechanisms.
Zaccone
Paola
P
Immunology Division, Department of Pathology, University of Cambridge, Cambridge, UK.
Raine
Tim
T
Sidobre
Stéphane
S
Kronenberg
Mitchell
M
Mastroeni
Pietro
P
Cooke
Anne
A
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000382:microbiology*; D005260:Female; D005434:Flow Cytometry; D006651:Histocytochemistry; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000382:microbiology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology
D015703:Antigens, CD; D016753:Interleukin-10; D007371:Interferon-gamma