Helicobacter hepaticus Cholesterol‐α‐glucosyltransferase is Essential for Establishing Colonization in Male A/JCr Mice. Issue 4 (23rd May 2014)

• Record Type: Journal Article
• Authors: Ge, Zhongming; Feng, Yan; Muthupalani, Sureshkumar; Whary, Mark T.; Versalovic, James; Fox, James G.
• Is Part Of: Helicobacter. Volume 19:Issue 4(2014:Aug.)
• Page Start: 280
• Page End: 288
• Publication Date: 2014-05-23
• Subjects: Helicobacter -- Periodicals; Helicobacter infections -- Periodicals; Stomach -- Diseases -- Periodicals; 616.3301405
• DOI: 10.1111/hel.12135
• Languages: English
• ISSNs: 1083-4389

Abstract

<abstract abstract-type="main" id="hel12135-abs-0001"> <title>Abstract</title> <sec id="hel12135-sec-0001" sec-type="section"> <title>Background</title> <p> <italic>Helicobacter pylori</italic> cholesterol‐α‐glucosyltransferase (<italic>cgt</italic>) is essential for survival of <italic>H. pylori</italic> in mice. Enterohepatic <italic>H. hepaticus, </italic> the cause of colonic and hepatocellular carcinoma in susceptible mouse strains, contains an ortholog of the <italic>H. pylori cgt</italic>. However, the role of <italic>cgt</italic> in the pathogenesis of <italic>H. hepaticus</italic> has not been investigated.</p> </sec> <sec id="hel12135-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p>Two <italic>cgt</italic>‐deficient isogenic mutants of wild‐type <italic>H. hepaticus</italic> (WT) 3B1 were generated and used to inoculate male A/JCr mice. Cecal and hepatic colonization levels of the mutants and WT 3B1 as well as select inflammation‐associated cytokines were measured by qPCR at 4 months postinoculation.</p> </sec> <sec id="hel12135-sec-0003" sec-type="section"> <title>Results</title> <p>Both mutants were undetectable in the cecum of any inoculated mice (10 per mutant) but were detected in two livers (one for each mutant); by contrast, 9 and 7 of 10 mice inoculated with WT 3B1 were qPCR positive in the ceca and livers, respectively. The mice inoculated with the mutants developed significantly less severe hepatic inflammation (<italic>p </italic><<italic> </italic>.05) and also produced significantly lower hepatic mRNA levels of proinflammatory cytokines Ifn‐γ (<italic>p </italic><<italic> </italic>.01) and Tnf‐α (<italic>p </italic>≤<italic> </italic>.02) as well as anti‐inflammatory factors Il10 and Foxp3 compared with the WT 3B1‐inoculated mice. Additionally, the WT 3B1‐inoculated mice developed significantly higher Th1‐associated IgG2a (<italic>p </italic><<italic> </italic>.0001) and Th2‐associated IgG1 responses (<italic>p </italic><<italic> </italic>.0001) to <italic>H. hepaticus</italic> infection than mice dosed with isogenic <italic>cgt</italic> mutants.</p> </sec> <sec id="hel12135-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Our data indicate that the cholesterol‐α‐glucosyltransferase is required for establishing colonization of the intestine and liver and therefore plays a critical role in the pathogenesis of <italic>H. hepaticus</italic>.</p> </sec> </abstract>