ABSTRACTTo investigate how different enterohepaticHelicobacterspecies (EHS) influenceHelicobacter pylorigastric pathology, C57BL/6 mice were infected withHelicobacter hepaticusorHelicobacter muridarum, followed byH. pyloriinfection 2 weeks later. Compared toH. pylori-infected mice, mice infected withH. muridarumandH. pylori(HmHp mice) developed significantly lower histopathologic activity index (HAI) scores (P< 0.0001) at 6 and 11 months postinoculation (MPI). However, mice infected withH. hepaticusandH. 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 ofH. 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 ofH. pylori-infected mice (P< 0.01). Coinfection withH. hepaticusalso suppressedH. pylori-induced elevation of gastric Th1 cytokinesIfn-γandTnf-α(P< 0.0001) but increased Th17 cytokine mRNA levels (P= 0.028) at 6 MPI. Furthermore, mRNA levels ofIl-17Awere 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 gastricH. pyloriwere 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 ofH. 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 toH. pyloriinfection.
Coinfection with Enterohepatic Helicobacter Species Can Ameliorate or Promote Helicobacter pylori-Induced Gastric Pathology in C57BL/6 Mice