Outbred mice with long-term Helicobacter felis infection develop both gastric lymphoid tissue and glandular hyperplastic lesions.
Experimental infection of mice with Helicobacter felis reproduces many aspects of the gastritis observed in Helicobacter pylori-infected humans. The development of gastric inflammatory lesions in chronically infected inbred mice is host-dependent; in BALB/c mice, gastric B-cell MALT lymphomas were observed, whilst other murine hosts (e.g. C57BL/6) developed severe glandular hyperplasia. The aims of this investigation were to characterize and immunophenotype Helicobacter-induced inflammatory lesions in mice with an outbred genetic background. Swiss mice (n=10 per group) were either inoculated with a suspension of H. felis or left untreated. H. felis-inoculated mice and age-matched control animals were killed 13 months later. The severity of gastric inflammatory lesions in the animals was graded and the number and distribution of B (CD45R(+)) and T (CD3(+)) lymphocytes in lymphoid tissues was determined by immunohistochemistry. Compared with control mice, animals with long-term H. felis infection developed severe hyperplastic gastritis (0.80+/-0.63 vs. 2.7+/-0.68), with epithelial dedifferentiation (0. 40+/-0.52 vs. 2.3+/-0.82) and lengthening of the pits and glands (0. 46+/-0.05 vs. 0.8+/-0.19). Gastric CD45R(+) and CD3(+) lymphocyte scores were significantly elevated (r=0.803) in infected animals, while lymphoepithelial lesions and polymorphonuclear leucocyte infiltrates were absent. Although prominent lymphoid follicles were present in the tissues of all infected animals, and in one control animal, only a proportion (55%) of the mucosal follicles had a dominant B-cell phenotype (defined as > or =75% CD45R(+) labelling), and all were poorly labelled with anti-mouse immunoglobulin antibodies. It was concluded that the lesions in outbred Swiss mice differed from B-cell MALT lymphomas. In contrast to inbred mice, outbred animals developed both glandular and lymphoid tissue lesions to chronic H. felis infection. It is suggested that the default T-helper phenotype of the host influences glandular lesion formation or B-cell lymphomagenesis in this model of infection.
Ferrero
R L
RL
Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, Paris Cedex 15, France. rferrero@pasteur.fr
Avé
P
P
Radcliff
F J
FJ
Labigne
A
A
Huerre
M R
MR
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology; D017252:CD3 Complex / Q000032:analysis; D002908:Chronic Disease; D005756:Gastritis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D006965:Hyperplasia / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007124:Immunoenzyme Techniques; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008221:Lymphoid Tissue / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000382:microbiology; D051379:Mice; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms; D013270:Stomach / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D017252:CD3 Complex; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D017493:Leukocyte Common Antigens