Escherichia coli infection induces autoimmune cholangitis and anti‐mitochondrial antibodies in non‐obese diabetic (NOD).B6 (Idd10/Idd18) mice. (February 2014)

• Record Type: Journal Article
• Authors: Wang, J. J.; Yang, G.‐X.; Zhang, W. C.; Lu, L.; Tsuneyama, K.; Kronenberg, M.; Véla, J. L.; Lopez‐Hoyos, M.; He, X.‐S.; Ridgway, W. M.; Leung, P. S. C.; Gershwin, M. E.
• Is Part Of: Clinical and experimental immunology. Volume 175:Number 2(2014:Feb.)
• Page Start: 192
• Page End: 201
• Publication Date: 2014-02
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12224
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Several epidemiological studies have demonstrated that patients with primary biliary cirrhosis (PBC) have a higher incidence of urinary tract infections (UTI) and there is significant homology of the immunodominant mitochondrial autoantigen, the E2 component of the pyruvate dehydrogenase complex (PDC‐E2), between mammals and bacteria. Previous work has demonstrated that non‐obese diabetic (NOD).B6 <italic>Idd10/Idd18</italic> infected with <italic>Novosphingobium aromaticivorans</italic> developed liver lesions similar to human PBC. It was postulated that the biliary disease was dependent upon the presence of the unique <italic>N. aro</italic> glycosphingolipids in activating natural killer T (NK T) cells. To address this issue, we infected NOD.B6 <italic>Idd10/Idd18</italic> mice with either <italic>Escherichia coli</italic>, <italic>N. aro</italic> or use of a phosphate‐buffered saline (PBS) vehicle control and serially followed animals for the appearance of liver pathology and anti‐mitochondrial autoantibodies (AMA). Of striking importance, the biliary disease of <italic>E. coli</italic>‐infected mice was more severe than <italic>N. Aro</italic>‐infected mice and the titre of AMA was higher in <italic>E. coli</italic>‐infected mice. Furthermore, the immunopathology did not correlate with the ability of bacterial extracts to produce antigen‐dependent activation of NK T cells. Our data suggest that the unique glycosphingolipids of <italic>N. aro</italic> are not required for the development of autoimmune cholangitis. Importantly, the data highlight the clinical significance of <italic>E. coli</italic> infection in a genetically susceptible host, and we suggest that the appearance of autoimmune cholangitis is dependent upon molecular mimicry. These data highlight that breach of tolerance to PDC‐E2 is probably the first event in the natural history of PBC in genetically susceptible hosts.</p> </abstract>