title: Colonization of C57BL/6J and BALB/c wild-type and knockout mice with Helicobacter pylori: effect of vaccination and implications for innate and acquired immunity.
abstract: The gram-negative bacterial pathogen Helicobacter pylori is a major cause of peptic ulcer disease and a risk factor for gastric cancer in humans. Adapted H. pylori strains, such as strain SS1, are able to infect mice and are a useful model for gastric colonization and vaccination studies. In this study we used a streptomycin-resistant derivative of H. pylori SS1 to analyze the colonization behavior and the success of vaccination in wild-type (wt) and various knockout mice of the BALB/c and C57BL/6J genetic backgrounds. We here report that BALB/c interleukin-4 knockout (IL-4(-/-)) mice are weakly overcolonized compared to the wt strain but that the IL-12(-/-) knockout results in a strong overcolonization (500%). Unexpectedly, in the C57BL/6J background the same knockouts behaved in diametrically opposed manners. The IL-4(-/-) mutation caused a 50% reduction and the IL-12(-/-) knockout caused a 95% reduction compared to the wt colonization rate. For C57BL/6J mice we further analyzed the IL-18(-/-) and Toll-like receptor 2 knockout mutations, which showed reductions to 66 and 57%, respectively, whereas mice with the IL-10(-/-) phenotype were hardly infected at all (5%). In contrast, the tumor necrosis factor receptor knockout (p55(-/-) and p55/75(-/-)) mice showed an overcolonization compared to the C57BL/6J wt strain. With exception of the low-level infected C57BL/6J IL-10(-/-) and IL-12(-/-) knockout mice, all knockout mutants were accessible to a prophylactic vaccination and their vaccination behavior was comparable to that of the wt strains.
authors.affiliation: Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Panthel
authors.forename: Gerhard
authors.initials: G
authors.lastname: Faller
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D029721:Drosophila Proteins; D005260:Female; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D016481:Helicobacter Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D007110:Immunity, Active; D007113:Immunity, Innate; D007114:Immunization; D007378:Interleukins / Q000172:deficiency / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000235:genetics; D013045:Species Specificity; D013270:Stomach / Q000382:microbiology / Q000473:pathology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
chemical_list: D001428:Bacterial Vaccines; D029721:Drosophila Proteins; D007378:Interleukins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors