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Innate Immune Pathways in Virus‐Induced Autoimmune Diabetes
Author(s) -
Nair Anjali,
Wolter Travis R.,
Meyers Adam J.,
Zipris Danny
Publication year - 2008
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1447.004
Subject(s) - innate immune system , downregulation and upregulation , tlr9 , tlr2 , stat protein , immune system , biology , microbiology and biotechnology , signal transduction , stat , immunology , stat3 , gene expression , biochemistry , dna methylation , gene
We recently hypothesized that Toll‐like receptor‐induced innate upregulation by Kilham rat virus (KRV) in the BioBreeding diabetes‐resistant (BBDR) rat model plays a key role in the mechanism of diabetes induction. To address this hypothesis, we analyzed innate immune signaling pathways upregulated by KRV in vitro and in vivo . We demonstrate that KRV activates the signal transducer and activator of transcription (STAT)‐1 in spleen cells in vitro and that this activation can be blocked by TLR9 inhibition. We also show that KRV upregulates STAT‐1 in pancreatic lymph nodes early after virus infection. Our data may implicate TLR9‐induced STAT‐1 signaling pathways in KRV‐induced innate immune activation in the BBDR rat and raise the possibility that these pathways are involved in mediating autoimmune diabetes.