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

Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences,¹ Kitasato Institute for Life Sciences & Graduate School of Infection Control Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan,² Center for Basic Research,³ Department of Internal Medicine, Kitasato Institute Hospital, The Kitasato Institute, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan,⁴ Third Department of Internal Medicine, Kyorin University, Mitaka, Tokyo 181-8611, Japan,⁵ Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan⁶

Received 12 September 2006/ Returned for modification 13 October 2006/ Accepted 14 December 2006

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.

Published ahead of print on 28 December 2006.

Editor: A. D. O'Brien

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