title: Coinfection with Enterohepatic Helicobacter species can ameliorate or promote Helicobacter pylori-induced gastric pathology in C57BL/6 mice.
abstract: To investigate how different enterohepatic Helicobacter species (EHS) influence Helicobacter pylori gastric pathology, C57BL/6 mice were infected with Helicobacter hepaticus or Helicobacter muridarum, followed by H. pylori infection 2 weeks later. Compared to H. pylori-infected mice, mice infected with H. muridarum and H. pylori (HmHp mice) developed significantly lower histopathologic activity index (HAI) scores (P < 0.0001) at 6 and 11 months postinoculation (MPI). However, mice infected with H. hepaticus and H. pylori (HhHp mice) developed more severe gastric pathology at 6 MPI (P = 0.01), with a HAI at 11 MPI (P = 0.8) similar to that of H. pylori-infected mice. H. muridarum-mediated attenuation of gastritis in coinfected mice was associated with significant downregulation of proinflammatory Th1 (interlukin-1beta [Il-1β], gamma interferon [Ifn-γ], and tumor necrosis factor-alpha [Tnf-α]) cytokines at both time points and Th17 (Il-17A) cytokine mRNA levels at 6 MPI in murine stomachs compared to those of H. pylori-infected mice (P < 0.01). Coinfection with H. hepaticus also suppressed H. pylori-induced elevation of gastric Th1 cytokines Ifn-γ and Tnf-α (P < 0.0001) but increased Th17 cytokine mRNA levels (P = 0.028) at 6 MPI. Furthermore, mRNA levels of Il-17A were positively correlated with the severity of helicobacter-induced gastric pathology (HhHp>H. pylori>HmHp) (at 6 MPI, r² = 0.92, P < 0.0001; at 11 MPI, r² = 0.82, P < 0.002). Despite disparate effects on gastritis, colonization levels of gastric H. pylori were increased in HhHp mice (at 6 MPI) and HmHp mice (at both time points) compared to those in mono-H. pylori-infected mice. These data suggest that despite consistent downregulation of Th1 responses, EHS coinfection either attenuated or promoted the severity of H. pylori-induced gastric pathology in C57BL/6 mice. This modulation was related to the variable effects of EHS on gastric interleukin 17 (IL-17) responses to H. pylori infection.
authors.affiliation: Division of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. zge@mit.edu
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Ge
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Sureshkumar
authors.initials: S
authors.lastname: Muthupalani
authors.forename: Laura Lemke
authors.initials: LL
authors.lastname: Eurell
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Taylor
authors.forename: Mark T
authors.initials: MT
authors.lastname: Whary
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D005756:Gastritis / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D016998:Helicobacter / Q000145:classification / Q000472:pathogenicity*; D016481:Helicobacter Infections / Q000150:complications* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D044923:Helicobacter hepaticus / Q000472:pathogenicity*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D012720:Severity of Illness Index; D013270:Stomach / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines