ArticleFrontiers in immunology2019
Norovirus Changes Susceptibility to Type 1 Diabetes by Altering Intestinal Microbiota and Immune Cell Functions.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 41 citations in OpenAlex.
- Immune dysregulation in type 2 diabetes mellitus: Implications for tuberculosis, COVID-19, and HIV/AIDS.Infectious medicine · 2025Review
- Guidance on Establishing Health Monitoring Panels for Laboratory Mice to Reflect Contemporary Pathogen Prevalence.Journal of the American Association for Laboratory Animal Science : JAALAS · 2025Review
- The systemic lupus erythematosus-associated NCF1Nature communications · 2025Article
- Immune repertoire profiling and T cell dysregulation in Peripheral Blood Mononuclear Cells of Type 2 diabetic patients.PloS one · 2025Article
- Intestinal Tuft Cells: Morphology, Function, and Implications for Human Health.Annual review of physiology · 2024Review
- Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10Frontiers in immunology · 2024Article
- Gut microbiome and NAFLD: impact and therapeutic potential.Frontiers in microbiology · 2024Review
- Pan-viral serology uncovers distinct virome patterns as risk predictors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma.Cell reports. Medicine · 2023Article
- Gastrointestinal Infections Modulate the Risk for Insulin Autoantibodies as the First-Appearing Autoantibody in the TEDDY Study.Diabetes care · 2023Article
- Recent Advances on Small-Molecule Antagonists Targeting TLR7.Molecules (Basel, Switzerland) · 2023Review
- Virus induced dysbiosis promotes type 1 diabetes onset.Frontiers in immunology · 2023Article
- Possible connection between intestinal tuft cells, ILC2s and obesity.Frontiers in immunology · 2023Review
- The role of virome in the gastrointestinal tract and beyond.FEMS microbiology reviews · 2022Review
- Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China.Open life sciences · 2022Article
- Microbial dysbiosis in the gut drives systemic autoimmune diseases.Frontiers in immunology · 2022Review
- Antibody Production Remains Intact Despite Loss of Bone Marrow B cells in Murine Norovirus InfectedComparative medicine · 2021Article
- Single-cell sequencing of rotavirus-infected intestinal epithelium reveals cell-type specific epithelial repair and tuft cell infection.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Interaction Between Viruses and Intestinal Microbiota: A Review.Current microbiology · 2021Review
- Enteric Tuft Cells in Host-Parasite Interactions.Pathogens (Basel, Switzerland) · 2021Review
- The dark side of the gut: Virome-host interactions in intestinal homeostasis and disease.The Journal of experimental medicine · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Environmental factors contribute to Type 1 diabetes (T1D) susceptibility. The gut microbiome, which includes bacteria, viruses, and fungi, contributes to this environmental influence, and can induce immunological changes. The gut viral component of the microbiome, related to T1D has mostly focused on coxsackieviruses and rotavirus. The role of norovirus, another common enteric virus, in susceptibility to T1D was hitherto unknown. Norovirus is highly infectious and encountered by many children. We studied the mouse norovirus 4 (MNV4), related to human noroviruses, in the Non-obese diabetic (NOD) mouse model, to determine its role in influencing susceptibility to T1D. We infected MNV-free NOD mice with MNV4 by exposing the mice to MNV4-positive bedding from an endemically-infected mouse colony to mimic a natural infection. Control MNV-free NOD mice were exposed to MNV-free bedding from the same colony. Interestingly, MNV4 infection protected NOD mice from the development of T1D and was associated with an expansion of Tregs and reduced proinflammatory T cells. We also found MNV4 significantly modified the gut commensal bacteria composition, promoting increased α-diversity and Firmicutes/Bacteroidetes ratio. To elucidate whether T1D protection was directly related to MNV4, or indirectly through modulating gut microbiota, we colonized germ-free (GF) NOD mice with the MNV4-containing or non-MNV4-containing viral filtrate, isolated from filtered fecal material. We found that MNV4 induced significant changes in mucosal immunity, including altered Tuft cell markers, cytokine secretion, antiviral immune signaling markers, and the concentration of mucosal antibodies. Systemically, MNV4-infection altered the immune cells including B cell subsets, macrophages and T cells, and especially induced an increase in Treg number and function. Furthermore,
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.