Helicobacter pylori infection does not promote hepatocellular cancer in a transgenic mouse model of hepatitis C virus pathogenesis.
Helicobacter pylori (H. pylori) and hepatitis C virus (HCV) infect millions of people and can induce cancer. We investigated if H. pylori infection promoted HCV-associated liver cancer. Helicobacter-free C3B6F1 wild-type (WT) and C3B6F1-Tg(Alb1-HCVN)35Sml (HT) male and female mice were orally inoculated with H. pylori SS1 or sterile media. Mice were euthanized at ~12 mo postinoculation and samples were collected for analyses. There were no significant differences in hepatocellular tumor promotion between WT and HT mice; however, HT female mice developed significantly larger livers with more hepatic steatosis than WT female mice. H. pylori did not colonize the liver nor promote hepatocellular tumors in WT or HT mice. In the stomach, H. pylori induced more corpus lesions in WT and HT female mice than in WT and HT male mice, respectively. The increased corpus pathology in WT and HT female mice was associated with decreased gastric H. pylori colonization, increased gastric and hepatic interferon gamma expression, and increased serum Th1 immune responses against H. pylori. HT male mice appeared to be protected from H. pylori-induced corpus lesions. Furthermore, during gastric H. pylori infection, HT male mice were protected from gastric antral lesions and hepatic steatosis relative to WT male mice and these effects were associated with increased serum TNF-α. Our findings indicate that H. pylori is a gastric pathogen that does not promote hepatocellular cancer and suggest that the HCV transgene is associated with amelioration of specific liver and gastric lesions observed during concurrent H. pylori infection in mice.
Division of Comparative Medicine; Massachusetts Institute of Technology; Cambridge MA USA.
Alexis
A
García
Division of Comparative Medicine; Massachusetts Institute of Technology; Cambridge MA USA.
Yan
Y
Feng
Division of Comparative Medicine; Massachusetts Institute of Technology; Cambridge MA USA.
Nicola M A
NM
Parry
Division of Comparative Medicine; Massachusetts Institute of Technology; Cambridge MA USA.
Amanda
A
McCabe
Division of Comparative Medicine; Massachusetts Institute of Technology; Cambridge MA USA.
Melissa W
MW
Mobley
Division of Comparative Medicine; Massachusetts Institute of Technology; Cambridge MA USA.
Kvin
K
Lertpiriyapong
Division of Comparative Medicine; Massachusetts Institute of Technology; Cambridge MA USA.
Mark T
MT
Whary
Division of Comparative Medicine; Massachusetts Institute of Technology; Cambridge MA USA.
James G
JG
Fox
D000818:Animals; D060085:Coinfection / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000473:pathology* / Q000821:virology; D016480:Helicobacter pylori; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications / Q000382:microbiology / Q000473:pathology*; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000382:microbiology; D008113:Liver Neoplasms / Q000382:microbiology / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size; D013270:Stomach / Q000382:microbiology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
Hepatitis; bacteria; cancer; helicobacter; infection; mice; transgenic; virus