Gastric B‐cell mucosa‐associated lymphoid tissue (MALT) lymphoma in an animal model of ‘Helicobacter heilmannii’ infection

Abstract

While Helicobacter pylori is accepted as the dominant human gastric bacterial pathogen, a small percentage of human infections have been associated with another organism, commonly referred to as 'Helicobacter heilmannii', which is more prevalent in a range of animal species. This latter bacterium has been seen in association with the full spectrum of human gastric diseases including gastritis, peptic ulceration, and gastric carcinomas, including gastric B-cell mucosa-associated lymphoid tissue (MALT) lymphoma. This study describes an analysis of the pathogenic potential of a number of 'H heilmannii' isolates in an animal model of gastric MALT lymphoma. BALB/c mice were infected with ten different 'H heilmannii' isolates originating from both human and animal hosts. The animals were examined at various time points for up to 28 months after infection. The infected animals initially developed a chronic inflammatory response within 6 months. This histological response increased in severity with the length of infection, with the development of overt lymphoma in some animals 18 months after infection. MALT lymphomas were detected in up to 25% of the infected animals. The prevalence of lymphoma was dependent on the length of infection and the origin of the infecting isolates. A range of other histological features accompanied the lymphocytic infiltration, including invaginations of the gastric epithelium and associated hyperplastic tissue, mucus metaplasia, and a small number of diffuse large B-cell lymphomas. The ability to manipulate experientially the presence of the bacterium in the animal model will allow further studies examining the role of antigen drive in the development of Helicobacter-associated MALT lymphoma.

“ Candidatus Helicobacter heilmannii” from a Cynomolgus Monkey Induces Gastric Mucosa-Associated Lymphoid Tissue Lymphomas in C57BL/6 Mice

“…The difference between the length of the period before MALT lymphoma occurrence in the study of O'Rourke et al (19) and the length of the period in our study may have been due to differences between the experimental animals and the bacteria used. When the animal species used in the studies are considered, the differences may have resulted from the Th1/2 status of the Th1-predominant C57BL/6 mice and the Th2-predominant BALB/c mice.…”

“…In addition, Bcl-X-immunoreactive cells were found in these mice 6 and 12 months later. O'Rourke and colleagues reported finding "Candidatus Helicobacter heilmannii"-associated gastric MALT lymphomas in normal BALB/c mice; furthermore, 15 months after infection with "Candidatus Helicobacter heilmannii"-like isolates from bobcats and other animals, they reported finding lymphoepithelial lesions in up to 80% of the mice, and at 18 months after infection they found lymphomas in up to 25% of the mice (19). The present study clearly demonstrated that "Candidatus Helicobacter heilmannii" infection with cynomolgus monkey mucosal and mucous homogenates resulted in MALT lymphoma formation in 50% of the C57BL/6 mice 3 months after infection and in 100% of the animals 6 months after infection; therefore, this could be a useful animal model of gastric MALT lymphomas, provided that these bacilli can be successfully cultured.…”

“…In animal models, MALT lymphomas have been reported following infection with Helicobacter mustelae in ferrets (7), following infection with Helicobacter felis in normal BALB/c mice (6), following infection with H. pylori in neonatally thymectomized BALB/c mice (9), and following infection with "Candidatus Helicobacter heilmannii" in normal BALB/c mice (19,21). In this study, we used the "Candidatus Helicobacter heilmannii" previously obtained from a cynomolgus monkey to infect C57BL/6 mice for up to 24 months.…”

Helikobakter Enfeksiyonlu Köpeklerde Demir Yetmezliği Anemisinin Belirlenmesi

“…Scientists have focused on the essential information that belongs to the bacterium for the last 20 years [8,14,17] . There are evidences on the fact that helicobacter infections cause iron deficiency [11][12][13][14][15][16] .…”

“…Recently, O' Rourke et al [8] have managed to distinguish H. felis, H. salomonis, H. bizzozeronii and H. heilmannii by conducting sequence analysis of a part of urease gene complex. In subsequent studies, it has been found out that H. pylori experimentally causes a similar disease in dogs [7] , but Helicobacter is a frequent infection an dogs [9,10] .…”