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Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice

Hu, Youjia, Jin, Ping, Peng, Jian, Zhang, Xiaojun, Wong, Florence Susan and Wen, Li 2016. Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice. Journal of Autoimmunity 72 , pp. 47-56. 10.1016/j.jaut.2016.05.001

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Type 1 diabetes; Gut microbiota; Antibiotic treatment
Publisher: Elsevier
ISSN: 0896-8411
Date of First Compliant Deposit: 21 November 2016
Date of Acceptance: 2 May 2016
Last Modified: 11 Jul 2017 09:33
URI: http://orca.cf.ac.uk/id/eprint/96321

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