Helicobacter hepaticus HHGI1 is a pathogenicity island associated with typhlocolitis in B6.129-IL10tm1Cgn mice

Helicobacter hepaticus strain 313 1 (H. hepaticus) contains a genomic island of similar to 71 kb, HHGI1, with some of the common features shared among known bacterial pathogenicity islands. In this study, we characterized the pathogenic potential of HHGI1 by infecting 136.129-IL10(tm1Cgn) (ILIO-/-) mice with an isogenic mutant (namely HhPAId1) lacking 19 predicted genes within HHGII. In contrast to H. hepaticus (P < 0.001), HhPAId1 did not cause typhlocolitis and hyperplasia in IL10(-/-) mice. Colonization levels of HhPAId1 were significantly higher in the cecum (P < 0.007) and similar in the colon (P = 0.27) when compared to H. hepaticus by 13 or 16 weeks post inoculation (WPI). The magnitude of the Th1-associated IgG2c response against HhPAId1 was less than that against H. hepaticus (P < 0.004). There was no significant difference in Th2-associated IgG1 responses against these two strains. Cecal and colonic mRNA levels of proinflammatory cytokines IFN-gamma, TNF-alpha and IL-17a in the HhPAId1-infected mice were significantly lower than those in the H. hepaticus-infected mice (P < 0.05) at 13 WPI. These results demonstrate that genes in the HHGI1 contribute to the pathogenicity of H. hepaticus, at least in part via up-regulation of proinflammatory mediators IFN-gamma, TNF-alpha and IL-17a. (C) 2008 Elsevier Masson SAS. All rights reserved.