Liver Autoimmunity Triggered by Microbial Activation of Natural Killer T Cells
Author Information
Author(s): Mattner Jochen, Savage Paul B., Leung Patrick, Oertelt Sabine S., Wang Vivien, Trivedi Omita, Scanlon Seth T., Pendem Krishna, Teyton Luc, Hart John, Ridgway William M., Wicker Linda S., Gershwin M. Eric, Bendelac Albert
Primary Institution: Howard Hughes Medical Institute, University of Chicago
Hypothesis
NKT cell recognition of N. aromaticivorans in the liver might be involved in liver pathology in PBC patients.
Conclusion
Infection with N. aromaticivorans can induce chronic liver disease resembling primary biliary cirrhosis in mice, mediated by NKT cells and T cells.
Supporting Evidence
- Infection of mice with N. aromaticivorans induced signature antibodies against microbial PDC-E2.
- Disease induction required NKT cells, which respond to N. aromaticivorans cell wall components.
- Once established, liver disease could be transferred by T cells independently of NKT cells.
- NOD 1101 mice exhibited severe liver enlargement and chronic bile duct lesions after infection.
- Chronic liver inflammation depended on CD1d and NKT cells.
- Early antibiotic treatment prevented chronic liver inflammation and autoantibody production.
- Transfer of splenocytes from infected mice induced liver disease in naive recipients.
Takeaway
When mice were infected with a certain bacteria, it caused their immune system to attack their own liver, similar to a disease in humans.
Methodology
Mice were infected with N. aromaticivorans, and their immune responses were monitored over several months.
Potential Biases
Potential bias in the interpretation of the immune response due to the specific mouse strains used.
Limitations
The study did not detect severe fibrosis in the mouse model, which is a characteristic of human PBC.
Participant Demographics
Mice used in the study included common strains such as C57BL/6, NOD, and SJL.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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