<i>Schistosoma mansoni</i> antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes

European Journal of Immunology - Tập 33 Số 5 - Trang 1439-1449 - 2003
Paola Zaccone1, Zoltán Fehérvári1, Frances M. Jones2, Stéphane Sidobre3, Mitchell Kronenberg3, David W. Dunne2, Anne Cooke1
1Immunology Division, Department of Pathology, University of Cambridge, Cambridge, GB.
2Microbiology and Parasitology Division, Department of Pathology, University of Cambridge, Cambridge, GB
3Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, USA

Tóm tắt

AbstractInfection 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 Vα14i 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.

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Tài liệu tham khảo

10.1538/expanim1978.29.1_1

10.1007/s00125-002-0781-1

10.1126/science.3277269

10.1084/jem.171.6.2091

Baxter A., 1994, Mycobacteria precipitate an SLE‐like syndrome in diabetes‐prone NOD mice., Immunology, 83, 227

10.1046/j.1365-3024.1999.00213.x

10.1136/bmj.299.6710.1259

10.1007/s00125-002-0801-1

Kullberg M. C., 1992, Infection with Schistosoma mansoni alters Th1/Th2 cytokine responses to a non‐parasite antigen., J. Immunol., 148, 3264, 10.4049/jimmunol.148.10.3264

10.1086/338574

10.1038/nm0901-1052

10.1038/nm0901-1057

Makaaru C. K., 1992, The human blood fluke Schistosoma mansoni synthesizes a novel type of glycosphingolipid., J. Biol. Chem., 267, 2251, 10.1016/S0021-9258(18)45870-X

10.4049/jimmunol.167.11.6087

Sher A., 1986, Induction of protective immunity against Schistosoma mansoni by a nonliving vaccine. IV. Fractionation and antigenic properties of a soluble adult worm immunoprophylactic activity., J. Immunol., 136, 3878, 10.4049/jimmunol.136.10.3878

10.1002/eji.1830260143

Okano M., 1999, Induction of Th2 responses and IgE is largely due to carbohydrates functioning as adjuvants on Schistosoma mansoni egg antigens., J.Immunol., 163, 6712, 10.4049/jimmunol.163.12.6712

Velupillai P., 1997, B‐1 cell (CD5+B220+) outgrowth in murine schistosomiasis is genetically restricted and is largely due to activation by polylactosamine sugars., J. Immunol., 158, 338, 10.4049/jimmunol.158.1.338

10.1016/0952-7915(95)80112-X

Baxter A. G., 1997, Association between alphabetaTCR+CD4–CD8– T cell deficiency and IDDM in NOD/Lt mice., Diabetes, 46, 572, 10.2337/diab.46.4.572

10.1002/eji.1830261226

10.1084/jem.187.7.1047

10.1073/pnas.251531798

10.3109/08916930108994121

10.1038/ni827

10.1016/S1074-7613(02)00473-9

10.1084/jem.192.5.741

10.4049/jimmunol.167.3.1164

10.1111/j.1365-3083.1994.tb03419.x

10.1006/expr.1996.0102

10.4049/jimmunol.168.2.537

10.1084/jem.194.3.313

10.1073/pnas.121169698

10.4049/jimmunol.169.2.906

10.1002/eji.1830220622

10.1016/S0022-1759(02)00204-1

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European Journal of Immunology

Tập 33 Số 5

1439-1449

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