Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes.
Infection with Schistosoma mansoni (S. mansoni) or exposure to eggs from this helminth inhibits the development of type 1 diabetes in NOD mice. In this study we show that soluble extracts of S. mansoni worm or egg completely prevent onset of type 1 diabetes in these mice but only if injection is started at 4 weeks of age. T cells from diabetes-protected mice make IL-10 in recall responses to parasite antigens. These cells are furthermore impaired in their ability to transfer diabetes to NOD-SCID recipients. Bone marrow dendritic cells derived from NOD mice are found to make more IL-10 and less IL-12 following culture with S. mansoni soluble egg antigens in conjunction with lipopolysaccharides. NOD mice are deficient in NKT cells. Soluble worm and egg antigens increase the numbers of V alpha 14i NKT cells in NOD mice. These effects of schistosome antigens on the innate immune system provide a mechanism for their ability to prevent type 1 diabetes in NOD mice.
Immunology Division, Department of Pathology, University of Cambridge, Cambridge, GB.
Paola
P
Zaccone
Zoltán
Z
Fehérvári
Frances M
FM
Jones
Stéphane
S
Sidobre
Mitchell
M
Kronenberg
David W
DW
Dunne
Anne
A
Cooke
D000818:Animals; D000947:Antigens, Helminth / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010063:Ovum / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
D000947:Antigens, Helminth; D016207:Cytokines; D016753:Interleukin-10