title: Attenuation ofHelicobacter pylori-induced gastric inflammation by priorcag-strain (AM1) infection in C57BL/6 mice.
abstract: BACKGROUND
  Helicobacter pylori,colonize in stomach of ~50% of the world population.cagpathogenicity Island ofH. pyloriis one of the important virulent factors that attributed to gastric inflammation. Coinfection withH. pyloristrain with different genetic makeup alters the degree of pathogenicity and susceptibility towards antibiotics. The present study investigates host immunomodulatory effects ofH. pyloriinfection by bothcag+strain (SS1) andcag-strain (AM1). C57BL/6 mice were infected with AM1 or SS1 strain as well as AM1 followed by SS1 (AM1/SS1) and vice versa.
  
  
  RESULTS
  Mice 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.
  
  
  CONCLUSIONS
  These data suggested that priorH. pylori cag-strain infection attenuated the severity of gastric pathology induced by subsequentcag+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-virulentH. pyloristrain (AM1) causes reduction of subsequent virulent strain (SS1) infection by regulation of inflammatory cytokines and MMPs expression.
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullik Road, Jadavpur, Kolkata, 700032 India.
authors.forename: Nillu
authors.initials: N
authors.lastname: Ghosh
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Prachetash
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullik Road, Jadavpur, Kolkata, 700032 India.
authors.forename: Kousik
authors.initials: K
authors.lastname: Kesh
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Asish K
authors.initials: AK
authors.lastname: Mukhopadhyay
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullik Road, Jadavpur, Kolkata, 700032 India.
authors.forename: Snehasikta
authors.initials: S
authors.lastname: Swarnakar
keywords: Cag pathogenicity island; Coinfection; Cytokine; Gastric ulcer; Helicobacter pylori; Immunosuppression; Inflammation; MMP