Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice. (August 2016)

• Record Type: Journal Article
• Authors: Hu, Youjia; Jin, Ping; Peng, Jian; Zhang, Xiaojun; Wong, F. Susan; Wen, Li
• Is Part Of: Journal of autoimmunity. Volume 72(2016)
• Page Start: 47
• Page End: 56
• Publication Date: 2016-08
• Subjects: Type 1 diabetes -- Gut microbiota -- Antibiotic treatment; T1D type 1 diabetes -- HLA human leukocyte antigen -- IDDM1 insulin-dependent diabetes mellitus 1 -- NOD non-obese diabetic -- TCR T cell receptor -- Neo neomycin -- Van vancomycin -- ICC intracellular cytokine -- PMA Phorbol 12-myristate 13-acetate -- SI stimulation index -- SPL spleen -- MLN mesenteric lymph nodes -- PLN pancreatic lymph nodes -- PP Peyer's patches -- APC antigen presenting cell -- DC dendritic cell -- IGRP islet-specific glucose-6-phosphatase catalytic subunit-related protein -- G+ Gram positive -- G− Gram negative; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2016.05.001
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Environmental factors clearly influence the pathogenesis of Type 1 diabetes, an autoimmune disease. We have studied gut microbiota as important environmental agents that could affect the initiation or progression of type 1 diabetes especially in the prenatal period. We used neomycin, targeting mainly Gram negative or vancomycin, targeting mainly Gram positive bacteria, to treat pregnant NOD mothers and to study autoimmune diabetes development in their offspring. Neomycin-treated offspring were protected from diabetes, while vancomycin-treated offspring had accelerated diabetes development, and both antibiotics caused distinctly different shifts in gut microbiota composition compared with the offspring from untreated control mice. Our study demonstrated that neomycin treatment of pregnant mothers leads to generation of immune-tolerogenic antigen-presenting cells (APCs) in the offspring and these APCs had reduced specific autoantigen-presenting function both in vitro and in vivo . Moreover, the protection from diabetes mediated by tolerogenic APCs was vertically transmissible to the second generation. In contrast, more diabetogenic inflammatory T cells were found in the lymphoid organs of the offspring from the vancomycin-treated pregnant mothers. This change however was not transmitted to the second generation. Our results suggested that prenatal exposure to antibiotic influenced gut bacterial composition at the earliest time point in life and is critical for consequent education of the immune system. As different bacteria can induce different immune responses, understanding these differences and how to generate self-tolerogenic APCs could be important for developing new therapy for type 1 diabetes. Highlights: Antibiotic treatment during pregnancy influences T1D development in offspring. Neomycin and Vancomycin treatment significantly change the gut microbiota. Neomycin treatment induces immunotolerogenic APCs and protects from diabetes. Vancomycin treatment induces inflammatory T cell increase, accelerating diabetes. Neomycin protection from diabetes is vertically transmissible.