Abstract
Type 1 diabetes (T1D) is an autoimmune disease that culminates in beta cell destruction in the pancreas and, subsequently, deficiency in insulin production. Cytokines play a crucial role in the development of diabetes, orchestrating the recruitment and action of immune cells, to not only destroy insulin-producing cells but also preserve them. Therefore, the aim of this study was to investigate the effect of orally administered Lactococcus lactis MG1363 FnBPA+ strains carrying plasmids encoding IL-4 and IL-10 in the streptozotocin- (STZ-) induced diabetes model and in nonobese diabetic (NOD) mice. The STZ-induced mice that were treated with combined bacterial strains carrying plasmids encoding IL-4 and IL-10 showed lower incidence of diabetes and more preserved pancreatic islets than the mice that received the individual bacterial strains. Combined administration of L. lactis MG1363 FnBPA+ (pValac::dts::IL-4) and L. lactis MG1363 FnBPA+ (pValac::IL-10) resulted in protection against diabetes in NOD mice. It was shown that the combined treatment with recombinant bacterial by oral route prevented hyperglycemia and reduced the pancreatic islets-destruction in NOD mice. In addition, increased levels of IL-4 and IL-10 in serum and pancreatic tissue revealed a systemic effect of the treatment and also favored an anti-inflammatory microenvironment. Reduced concentrations of IL-12 in pancreas were essential to the regulation of inflammation, resulting in no incidence of diabetes in treated NOD mice. Normal levels of intestinal sIgA after long-term treatment with the L. lactis strains carrying plasmids encoding IL-4 and IL-10 indicate the development of oral tolerance and corroborate the use of this potent tool of mucosal delivery. For the first time, L. lactis MG1363 FnBPA+ strains carrying eukaryotic expression vectors encoding IL-4 and IL-10 are tested in STZ-induced and NOD mouse models. Therefore, our study demonstrates this innovative strategy provides immunomodulatory potential for further investigations in T1D and other autoimmune diseases.
Highlights
Type 1 diabetes (T1D) is a chronic immune-mediated disease characterized by destruction of β cells, the insulin-producing cells in the pancreas
We examined the effect of oral administration of L. lactis MG1363 fibronectin-binding protein A (FnBPA)+ and L. lactis MG1363 FnBPA+ in the two most extensively used animal models of T1D, the STZ-induced model, and nonobese diabetic (NOD) mice
The F-IL-4/IL-10-STZ group exhibited the highest percentage of nondiabetic mice (37%)
Summary
Type 1 diabetes (T1D) is a chronic immune-mediated disease characterized by destruction of β cells, the insulin-producing cells in the pancreas. Trafficking of autoreactive T lymphocytes to the pancreatic islets and the resulting inflammatory environment culminates in disease establishment in at-risk individuals [1]. 19 million people have T1D worldwide, and this number has increased over the years [2]. Lifelong administration of exogenous insulin is required, and this is the only therapy currently available. These individuals have to learn how to manage their condition and be aware of the possible disease-related complications. To study the pathogenesis and immunophysiology of T1D, some murine models have been developed over the Journal of Diabetes Research
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
