Male Syrian Hamsters Experimentally Infected with Helicobacter spp. of the H.bilis Cluster Develop MALT-Associated Gastrointestinal Lymphomas.

Abstract

Aged hamsters naturally infected with novel Helicobacter spp. classified in the H.bilis cluster develop hepatobiliary lesions and typhlocolitis. To determine whether enterohepatic H. spp. contribute to disease, Helicobacter-free hamsters were experimentally infected with H. spp. after suppression of intestinal bacteria by tetracycline treatment of dams and pups. After antibiotic withdrawal, weanlings were gavaged with four H.bilis-like Helicobacter spp. isolated from hamsters or H.bilis ATCC 43879 isolated from human feces and compared to controls (n=7 per group). Helicobacter bilis 43879-dosed hamsters were necropsied at 33 weeks postinfection (WPI) due to the lack of detectable infection by fecal PCR; at necropsy, 5 of 7 were weakly PCR positive but lacked intestinal lesions. The remaining hamsters were maintained for ~95 WPI; chronic H. spp. infection in hamsters (6/7) was confirmed by PCR, bacterial culture, fluorescent insitu hybridization, and ELISA. Hamsters had mild-to-moderate typhlitis, and three of the male H. spp.-infected hamsters developed small intestinal lymphoma, in contrast to one control. Of the three lymphomas in H. spp.-infected hamsters, one was a focal ileal mucosa-associated lymphoid tissue (MALT) B-cell lymphoma, while the other two were multicentric small intestinal large B-cell lymphomas involving both the MALT and extra-MALT mucosal sites with lymphoepithelial lesions. The lymphoma in the control hamster was a diffuse small intestinal lymphoma with a mixed population of T and B cells. Results suggest persistent H. spp. infection may augment riskfor gastrointestinal MALT origin lymphomas. This model is consistent with H.pylori/heilmannii-associated MALT lymphoma in humans and could be further utilized to investigate the mechanisms of intestinal lymphoma development.