| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Medicine and
Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655
Virus infection is hypothesized to be an important environmental "trigger" of type 1 diabetes in humans. We used the BBDR rat model to investigate the relationship between viral infection and autoimmune diabetes. BBDR rats are diabetes-free in viral Ab-free housing, but the disease develops in 
30% of BBDR rats infected with Kilham rat virus (KRV) through a process that does not involve infection of pancreatic 
cells. Pretreatment with polyinosinic-polycytidylic (poly(I:C)), a ligand of TLR3, acts synergistically to induce diabetes in 100% of KRV-infected rats. The mechanisms by which KRV induces diabetes and TLR3 ligation facilitates this process are not clear. In this study, we demonstrate that activation of the innate immune system plays a crucial role in diabetes induction. We report that multiple TLR agonists synergize with KRV infection to induce diabetes in BBDR rats, as do heat-killed Escherichia coli or Staphylococcus aureus (natural TLR agonists). KRV infection increases serum IL-12 p40 in a strain-specific manner, and increases IL-12 p40, IFN-
-inducible protein-10, and IFN- mRNA transcript levels, particularly in the pancreatic lymph nodes of BBDR rats. Infection with vaccinia virus or H-1 parvovirus induced less stimulation of the innate immune system and failed to induce diabetes in BBDR rats. Our results suggest that the degree to which the innate immune system is activated by TLRs is important for expression of virus-induced diabetes in genetically susceptible hosts.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  K. D. McCall, N. Harii, C. J. Lewis, R. Malgor, W. Bae Kim, M. Saji, A. D. Kohn, R. T. Moon, and L. D. Kohn High Basal Levels of Functional Toll-Like Receptor 3 (TLR3) and Noncanonical Wnt5a Are Expressed in Papillary Thyroid Cancer and Are Coordinately Decreased by Phenylmethimazole Together with Cell Proliferation and Migration Endocrinology, September 1, 2007; 148(9): 4226 - 4237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zipris, E. Lien, A. Nair, J. X. Xie, D. L. Greiner, J. P. Mordes, and A. A. Rossini TLR9-Signaling Pathways Are Involved in Kilham Rat Virus-Induced Autoimmune Diabetes in the Biobreeding Diabetes-Resistant Rat J. Immunol., January 15, 2007; 178(2): 693 - 701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-W. YOON and H.-S. JUN Viruses Cause Type 1 Diabetes in Animals Ann. N.Y. Acad. Sci., October 1, 2006; 1079(1): 138 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Roelofs, W. C. Boelens, L. A. B. Joosten, S. Abdollahi-Roodsaz, J. Geurts, L. U. Wunderink, B. W. Schreurs, W. B. van den Berg, and T. R. D. J. Radstake Identification of Small Heat Shock Protein B8 (HSP22) as a Novel TLR4 Ligand and Potential Involvement in the Pathogenesis of Rheumatoid Arthritis. J. Immunol., June 1, 2006; 176(11): 7021 - 7027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Fujinami, M. G. von Herrath, U. Christen, and J. L. Whitton Molecular Mimicry, Bystander Activation, or Viral Persistence: Infections and Autoimmune Disease Clin. Microbiol. Rev., January 1, 2006; 19(1): 80 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rasschaert, L. Ladriere, M. Urbain, Z. Dogusan, B. Katabua, S. Sato, S. Akira, C. Gysemans, C. Mathieu, and D. L. Eizirik Toll-like Receptor 3 and STAT-1 Contribute to Double-stranded RNA+ Interferon-{gamma}-induced Apoptosis in Primary Pancreatic {beta}-Cells J. Biol. Chem., October 7, 2005; 280(40): 33984 - 33991. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
