Attenuation of H-Pylori-Induced Gastric Pathology in C57bl/6 Mice by Co-Infection with Enterohepatic Helicobacters Is Helicobacter Species-Dependent

Abstract

To investigate how concurrent infection with an enterohepatic helicobacter species (EHS) affects H. pylori (Hp)-induced gastric pathology, C57BL/6 mice were inoculated with H. hepaticus (Hh), or H. muridarum (Hm), followed by infection with Hp. Compared to Hp-infected mice, HmHp-infected mice at 6 and 11 months postinoculation (mpi) had markedly attenuated histopathologic activity index (HAI) scores (P < 0.0001). By contrast, HhHp-infected mice had more severe HAI scores (P = 0.01) at 6 mpi and had similar HAI scores (P = 0.8) at 11 mpi when compared to Hp-infected mice. Hm-mediated attenuated pathology was associated with significant downregulation of proinflammatory Th1 (IL1, IFN[[Unsupported Character - &#61484;]] and TNF) and Th17 (IL-17A) cytokine mRNA levels in stomachs when compared to the Hp-infected mice. Although co-infection with Hh suppressed Hp-induced elevation of gastric Th1 cytokines, Th17 cytokine mRNA levels were increased. Colonization levels of gastric Hp were increased in both HhHp- and HmHp-infected mice compared to mono- Hp-infected mice. The Hp levels correlated with the mRNA levels of the gastric proinflammatory Th1 cytokines. Furthermore, the mRNA levels of IL17A were positively correlated with the severity of helicobacter-induced gastric pathology (HhHp>Hp> HmHp). Our data suggest: (1) host Th1 responses plays a major role in limiting Hp colonization; (2) EHS-mediated attenuation of the Hp-induced gastric pathology depends on the ability of the individual EHS to suppress both Th1 and IL17 proinflammatory pathways.