"Candidatus Helicobacter heilmannii" from a cynomolgus monkey induces gastric mucosa-associated lymphoid tissue lymphomas in C57BL/6 mice.
Both Helicobacter pylori and "Candidatus Helicobacter heilmannii" infections are associated with peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. However, good animal models of H. pylori clinical diseases are rare. In this study, we aimed to establish an animal model of "Candidatus Helicobacter heilmannii" gastric MALT lymphoma. We used a urease-positive gastric mucosal and mucus homogenate from a cynomolgus monkey maintained in C57BL/6 mouse stomachs. The bacterium in the homogenate was identified as "Candidatus Helicobacter heilmannii" based on a DNA sequence analysis of the 16S rRNA and urease genes. Mucosal and mucus homogenates were used to inoculate C57BL/6 mice, which were then examined for 24 months. We observed a gradual increase in the surface area of protrusive lesions in almost all infected C57BL/6 mouse fundic stomachs 6 months after infection. Light microscopic observations revealed an accumulation of B lymphocytes along with destruction of glandular elements and the presence of lymphoepithelial lesions consistent with low-grade MALT lymphomas. Electron microscopic observation revealed numerous "Candidatus Helicobacter heilmannii" bacilli in the fundic glandular lumen, the intracellular canaliculi, and the cytoplasm of intact cells, as well as damaged parietal cells. In conclusion, "Candidatus Helicobacter heilmannii" induced gastric MALT lymphomas in almost 100% of infected C57BL/6 mice after a 6-month period associated with the destruction of parietal cells.
Nakamura
Masahiko
M
School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. nakamuram@pharm.kitasato-u.ac.jp
Murayama
Somay Yamagata
SY
Serizawa
Hiroshi
H
Sekiya
Yukie
Y
Eguchi
Masahiro
M
Takahashi
Shinichi
S
Nishikawa
Kaori
K
Takahashi
Tetsufumi
T
Matsumoto
Tsukasa
T
Yamada
Haruki
H
Hibi
Toshifumi
T
Tsuchimoto
Kanji
K
Matsui
Hidenori
H
D000818:Animals; D005753:Gastric Mucosa / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000382:microbiology*; D018247:Helicobacter heilmannii / Q000235:genetics / Q000276:immunology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000382:microbiology* / Q000473:pathology; D008252:Macaca fascicularis; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008992:Monkey Diseases / Q000382:microbiology*; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology