Abstract
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the self-destruction of insulin-producing β cells. Recently, studies have revealed that neutrophils contribute to the early pathological injury to the pancreas, predominantly via the formation of neutrophil extracellular traps (NETs). To determine whether early intervention targeting NETs with staphylococcal nuclease (SNase) can delay the onset of T1DM, non-obese diabetic (NOD) mice were orally administered recombinant Lactococcus lactis (L. lactis) expressing SNase. The results showed that NETs were effectively disrupted by SNase both in vivo and in vitro, leading to a significant decrease in neutrophil-derived circulating free DNA (cf-DNA/NETs), neutrophil elastase (NE), and protease 3 (PR3) in the serum compared with the controls. In addition, SNase effectively regulated the blood glucose levels of NOD mice, and the onset of diabetes was postponed with reduced mortality and morbidity. Recombinant L. lactis also ameliorated inflammation in NOD mice, as evidenced by the remarkable increase in IL-4 and reductions in TNF-α and CRP. Moreover, HE staining results showed that L. lactis expressing SNase exerted protective effects on pancreatic islets and relieved inflammation of the small intestine in NOD mice. Hence, the present study indicates that the oral delivery of SNase by L. lactis can effectively prevent T1DM, ameliorate inflammation, and contribute to immunomodulatory balance in NOD mice.
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Acknowledgements
L. lactis strains were kindly provided by Professor Shuhua Tan, School of Life Science and Technology, China Pharmaceutical University. The English language of this article was edited by American Journal Experts.
Funding
This work was supported by the China National Natural Science Fund Committee (Grant Nos. 81172973 and 81673340), the National High Technology Research and Development Program of China (863 Program, No. 2015AA020314), the Jiangsu Provincial Natural Science Foundation of China (Grant No. BK20161462), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and institutional guidelines for the care and use of animals were followed.
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Lang, J., Wang, X., Liu, K. et al. Oral delivery of staphylococcal nuclease by Lactococcus lactis prevents type 1 diabetes mellitus in NOD mice. Appl Microbiol Biotechnol 101, 7653–7662 (2017). https://doi.org/10.1007/s00253-017-8480-5
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DOI: https://doi.org/10.1007/s00253-017-8480-5