Helicobacter hepaticus HHGI1 is a pathogenicity island associated with typhlocolitis in B6.129-IL10 tm1Cgn mice.
Helicobacter hepaticus strain 3B1 (H. hepaticus) contains a genomic island of approximately 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 B6.129-IL10 tm1Cgn (IL10-/-) mice with an isogenic mutant (namely HhPAId1) lacking 19 predicted genes within HHGI1. 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.
Ge
Zhongming
Z
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sterzenbach
Torsten
T
Whary
Mark T
MT
Rickman
Barry H
BH
Rogers
Arlin B
AB
Shen
Zeli
Z
Taylor
Nancy S
NS
Schauer
David B
DB
Josenhans
Christine
C
Suerbaum
Sebastian
S
Fox
James G
JG
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D002432:Cecum / Q000382:microbiology; D003092:Colitis / Q000382:microbiology*; D003106:Colon / Q000382:microbiology; D016207:Cytokines / Q000096:biosynthesis; D017353:Gene Deletion; D005798:Genes, Bacterial; D044404:Genomic Islands; D016481:Helicobacter Infections / Q000382:microbiology*; D044923:Helicobacter hepaticus / Q000235:genetics / Q000472:pathogenicity*; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000172:deficiency; D007413:Intestinal Mucosa / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014774:Virulence
D000907:Antibodies, Bacterial; D016207:Cytokines; D007074:Immunoglobulin G; D016753:Interleukin-10