| Autor: |
Matthew C. Funsten, Leonid A. Yurkovetskiy, Andrey Kuznetsov, Derek Reiman, Camilla H.F. Hansen, Katharine I. Senter, Jean Lee, Jeremy Ratiu, Shiva Dahal-Koirala, Dionysios A. Antonopoulos, Gary M. Dunny, Ludvig M. Sollid, David Serreze, Aly A. Khan, Alexander V. Chervonsky |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cell Host & Microbe. 31:213-227.e9 |
| ISSN: |
1931-3128 |
| Popis: |
Diet and commensals can affect the development of autoimmune diseases like type 1 diabetes (T1D). However, whether dietary interventions are microbe-mediated was unclear. We found that a diet based on hydrolyzed casein (HC) as a protein source protects non-obese diabetic (NOD) mice in conventional and germ-free (GF) conditions via improvement in the physiology of insulin-producing cells to reduce autoimmune activation. The addition of gluten (a cereal protein complex associated with celiac disease) facilitates autoimmunity dependent on microbial proteolysis of gluten: T1D develops in GF animals monocolonized with Enterococcus faecalis harboring secreted gluten-digesting proteases but not in mice colonized with protease deficient bacteria. Gluten digestion by E. faecalis generates T cell-activating peptides and promotes innate immunity by enhancing macrophage reactivity to lipopolysaccharide (LPS). Gnotobiotic NOD Toll4-negative mice monocolonized with E. faecalis on an HC + gluten diet are resistant to T1D. These findings provide insights into strategies to develop dietary interventions to help protect humans against autoimmunity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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