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Helicobacter hepaticus Cholesterol‐α‐glucosyltransferase is Essential for Establishing Colonization in Male A/ JC r Mice
Author(s) -
Ge Zhongming,
Feng Yan,
Muthupalani Sureshkumar,
Whary Mark T.,
Versalovic James,
Fox James G.
Publication year - 2014
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1111/hel.12135
Subject(s) - cecum , pathogenesis , mutant , biology , microbiology and biotechnology , wild type , inflammation , proinflammatory cytokine , immunology , gene , biochemistry , ecology
Abstract Background Helicobacter pylori cholesterol‐α‐glucosyltransferase ( cgt ) is essential for survival of H. pylori in mice. Enterohepatic H. hepaticus, the cause of colonic and hepatocellular carcinoma in susceptible mouse strains, contains an ortholog of the H. pylori cgt . However, the role of cgt in the pathogenesis of H. hepaticus has not been investigated. Materials and Methods Two cgt ‐deficient isogenic mutants of wild‐type H. hepaticus (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 q PCR at 4 months postinoculation. Results 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 q PCR positive in the ceca and livers, respectively. The mice inoculated with the mutants developed significantly less severe hepatic inflammation ( p < .05) and also produced significantly lower hepatic m RNA levels of proinflammatory cytokines Ifn‐γ ( p < .01) and Tnf‐α ( p ≤ .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 ( p < .0001) and Th2‐associated IgG1 responses ( p < .0001) to H. hepaticus infection than mice dosed with isogenic cgt mutants. Conclusion 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 H. hepaticus .