TLR‐2 agonist enhances the development of autoimmune diabetes

Abstract

Toll‐like receptor 2 agonist (TLR2) BLP (bacterial lipoprotein, PAM3CSV‐4) was found to enhance IL‐12 and INF‐α synthesis to ameliorate Th‐2 dependent pathology in experimental asthma and to modulate the functions of CD4+ CD25+ regulatory cells. TLR‐2 deficiency in NOD mice confers significant protection against the development of diabetes. Multiple low doses (40 mg/kg b.w) of streptozotocin given for 5 consecutive days, β‐cells (MLD‐STZ x 5 ) induce accumulation of apoptotic β cells and development of autoimmune diabetes in susceptible C57BL/6 male mice. However administration of 4 low doses of STZ (MLD‐STZ x 4) do not achieve such an effect and the number of apoptotic and necrotic cells was significantly lower by the end of (MLD‐STZ x 4) treatment than in (MLD‐STZ x 5) treated group. We have used (MLD‐STZ x 4) model to test the effect of TLR‐2 agonist on diabetes induction. We have clearly demonstrated that BLP facilitate diabetes induction when given in single daily i.p. injection of 200μg/mouse on days 5 – 10 after initiation of STZ treatment as evaluated by clinical and histological criteria. This enhancing effect was accompanied by the increased expression of TNF‐α, INF‐γ and IL‐17 in the draining pancreatic lymph nodes. The results are compatible with the notion that more effective presentation of islet specific autoantigens in TLR‐2 agonist treated group leads to autoimmune diabetes in this model. (Supported by UAE University Grant)