Attenuation of Helicobacter pylori-induced gastric inflammation by prior cag\u2212 strain (AM1) infection in C57BL/6 mice

Snehasikta Swarnakar,Asish K Mukhopadhyay,Prachetash Ghosh,Kousik Kesh,Nillu Ghosh

doi:10.1186/s13099-017-0161-5

Snehasikta Swarnakar, Asish K Mukhopadhyay + Show 3 more

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https://doi.org/10.1186/s13099-017-0161-5

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Abstract

BackgroundHelicobacter pylori, colonize in stomach of ~50% of the world population. cag pathogenicity Island of H. pylori is one of the important virulent factors that attributed to gastric inflammation. Coinfection with H. pylori strain with different genetic makeup alters the degree of pathogenicity and susceptibility towards antibiotics. The present study investigates host immunomodulatory effects of H. pylori infection by both cag+ strain (SS1) and cag− strain (AM1). C57BL/6 mice were infected with AM1 or SS1 strain as well as AM1 followed by SS1 (AM1/SS1) and vice versa.ResultsMice infected with AM1/SS1 strain exhibited less gastric inflammation and reduced proMMP9 and proMMP3 activities in gastric tissues as compared to SS1/SS1 and SS1/AM1 infected groups. The expression of both MMP9 and MMP3 followed similar trend like activity in infected tissues. Both Th1 and Th17 responses were induced by SS1 strain more profoundly than AM1 strain infection which induced solely Th1 response in spleen and gastric tissues. Moreover, IFN-γ, TNF-α, IL-1β and IL-12 were significantly downregulated in mice spleen and gastric tissues infected by AM1/SS1 compared to SS1/SS1 but not with SS1/AM1 coinfection. Surprisingly, IL-17 level was dampened significantly in AM1/SS1 compared to SS1/AM1 coinfected groups. Furthermore, number of Foxp3+ T-regulatory (Treg) cells and immunosuppressive cytokines like IL-10 and TGF-β were reduced in AM1/SS1 compared to SS1/SS1 and SS1/AM1 coinfected mice gastric tissues.ConclusionsThese data suggested that prior H. pylori cag− strain infection attenuated the severity of gastric pathology induced by subsequent cag+ strain in C57BL/6 mice. Prior AM1 infection induced Th1 cytokine IFN-γ, which reduced the Th17 response induced by subsequent SS1 infection. The reduced gastritis in AM1/SS1-infected mice might also be due to enrichment of AM1- primed Treg cells in the gastric compartment which inhibit Th1 and Th17 responses to subsequent SS1 infection. In summary, prior infection by non-virulent H. pylori strain (AM1) causes reduction of subsequent virulent strain (SS1) infection by regulation of inflammatory cytokines and MMPs expression.

Highlights

Helicobacter pylori, colonize in stomach of ~50% of the world population. cag pathogenicity Island of H. pylori is one of the important virulent factors that attributed to gastric inflammation
Prior cag− H. pylori infection dampens gastric inflammation due to cag+ H. pylori infection We previously reported that both cag+ strains (SS1) and cag− strain (AM1) has the capacity to induce gastric inflammation, the severity of damage was more pronounced in SS1 infection in C57BL/6 mice [26]
We investigated the coinfection of different strains of H. pylori in different combination on disease burden of H. pylori induced gastric pathology in C57BL/6 mice

Summary

Introduction

Helicobacter pylori, colonize in stomach of ~50% of the world population. cag pathogenicity Island of H. pylori is one of the important virulent factors that attributed to gastric inflammation. The present study investigates host immunomodulatory effects of H. pylori infection by both cag+ strain (SS1) and cag− strain (AM1). Strains harboring the cag PAI have been associated with more severe inflammatory responses than that induced by cag− strains [6, 8, 9]. H. pylori induced inflammation are associated with the production of pro-inflammatory cytokines and appear to be triggered partly by genes located within the cag PAI [6, 8, 12]. Earlier studies revealed that H. pylori infection is associated with a marked increased in cytokine IL-17 secretion from Th17 cells [14]. CagA and type IV secretion system are required for the induction of IL-17 responses in H. pylori infection [18]. Secretion of IL-17 led to induction of other inflammatory molecules required for the establishment of chronic inflammation [19]

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