Abstract
Non-obese diabetes (NOD) mice are widely used as an animal model in studies of type I diabetes (TID). Treatment with complete Freund's adjuvant (CFA) in pro-diabetic NOD mice is known to inhibit disease progression by activating CD1d-specific natural killer (NK) T cells and inducing interleukin (IL)-17 secretion in innate immune cells. The aim of the present study was to examine the effect of incomplete Freund's adjuvant (IFA) and L. monocytogenes treatment on the development of TID in NOD mice. This combined treatment of IFA and L. monocytogenes, a microbe that infects the liver and is primarily combatted by NK and cytotoxic T lymphocytes, was applied to mimic CFA treatment in pro-diabetic NOD mice. The combined IFA + L. monocytogenes treatment effectively delayed TID development in the NOD mice. In contrast to CFA, the IFA + L. monocytogenes treatment did not induce T cells or innate immune cells to secrete IL-17. However, increased levels of regulatory T cells were detected. Furthermore, IFA + L. monocytogenes mice exhibited higher levels of IgG2a, although no notable T helper 1 cell response was observed when compared with the CFA or IFA control treated mice. Therefore, combined IFA + L. monocytogenes treatment was shown to delay TID development in NOD mice via a novel mechanism, which was independent from the secretion of IL-17 by CFA-activated NKT cells.