title: Quantitative evaluation of inflammatory and immune responses in the early stages of chronic Helicobacter pylori infection.
abstract: The early consequences of Helicobacter pylori infection and the role of bacterial virulence determinants in disease outcome remain to be established. The present study sought to measure the development of host inflammatory and immune responses and their relationship to the putative bacterial virulence factors cag pathogenicity island (cagPAI), vacA allele, and oipA in combination with bacterial colonization density in a feline model of the early stages of H. pylori infection. Gastric tissues obtained from infected and uninfected cats were evaluated for H. pylori ureB, cagPAI, vacA allele, and oipA and colonization density (urease, histology, and real-time PCR). Inflammation was assessed by measuring mRNA upregulation of gamma interferon (IFN-gamma), interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, and IL-12 p40 and histopathology. The mucosal immune response was characterized by morphometric analysis of lymphoid follicles and by differentiating lymphocyte populations with antibodies against surface markers. Infecting H. pylori strains were positive for vacAs1 but lacked cagPAI and an active oipA gene. Colonization density was uniform throughout the stomach. Upregulation of IFN-gamma, IL-1 alpha, IL-1 beta, and IL-8 and increased severity of inflammatory infiltrates and fibrosis were observed in infected cats. The median number and total area of lymphoid aggregates were 5 and 10 times greater, respectively, in the stomachs of infected than uninfected cats. Secondary lymphoid follicles in uninfected cats were rare and positive for BLA.36 and B220 but negative for CD3 and CD79 alpha, whereas in infected cats they were frequent and positive for BLA.36, CD79 alpha, and CD3 but negative for B220. Upregulation of IFN-gamma, IL-1 alpha, IL-1 beta, and IL-8 and marked hyperplasia of secondary lymphoid follicles are early consequences of H. pylori infection in cats. The response appears to be similar to that of infected people, particularly children, can develop independently of the pathogenicity factors cagPAI and oipA, and is not correlated with the degree of colonization density or urease activity.
authors.affiliation: College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Reinhard K
authors.initials: RK
authors.lastname: Straubinger
authors.forename: Andrea
authors.initials: A
authors.lastname: Greiter
authors.forename: Sean P
authors.initials: SP
authors.lastname: McDonough
authors.forename: Alexander
authors.initials: A
authors.lastname: Gerold
authors.forename: Eugenio
authors.initials: E
authors.lastname: Scanziani
authors.forename: Sabina
authors.initials: S
authors.lastname: Soldati
authors.forename: Daiva
authors.initials: D
authors.lastname: Dailidiene
authors.forename: Giedrius
authors.initials: G
authors.lastname: Dailide
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Berg
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Simpson
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis; D001426:Bacterial Proteins / Q000032:analysis; D002415:Cats; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity; D006965:Hyperplasia; D016130:Immunophenotyping; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D012333:RNA, Messenger; C080866:cagA protein, Helicobacter pylori