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Infection and Immunity, April 1999, p. 1798-1805, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human Embryonic Gastric Xenografts in Nude Mice: a New Model of Helicobacter pylori Infection

Alain Lozniewski,1,* Filipe Muhale,2 Renee Hatier,3,4 Armelle Marais,5 Marie-Christine Conroy,1 Danielle Edert,1 Alain le Faou,1 Michele Weber,1 and Adrien Duprez2

Laboratoire de Bactériologie-Virologie UMR CNRS 75-65,1 Laboratoire d'Anatomie Pathologique,2 EP CNRS 616,3 and Laboratoire de Microscopie Electronique,4 Faculté de Médecine, 54505 Vandoeuvre-les-Nancy, and Laboratoire de Bactériologie, Université Victor Ségalen,5 33076 Bordeaux Cedex, France

Received 19 August 1998/Returned for modification 28 October 1998/Accepted 6 January 1999

In vitro or animal models have been used to investigate the pathogenesis of Helicobacter pylori infection. However, extrapolation to humans of results obtained with these heterologous models remains difficult. We have developed a new model for the study of H. pylori infection that uses human entire embryonic stomachs engrafted in nude mice. At 80 days after implantation, 22 of these xenografts, which exhibited a mature gastric epithelium, were inoculated with 107 to 108 CFU of either H. pylori LB1, a freshly isolated H. pylori strain (n = 12), or H. pylori ATCC 49503 (n = 10). After 12-week examination, H. pylori LB1 persistently colonized the antrum of all inoculated grafts, as assessed by culture (mucus and mucosa), immunohistochemistry (mucosa), and a rapid urease test (mucus). H. pylori ATCC 49503, either before or after in vivo passage, permitted only a transient 2-week colonization in one of the five inoculated grafts in both groups. Colonization was always associated with an increase of gastric juice pH. A mild neutrophil infiltration of the gastric mucosa was noted solely in infected grafts. Transmission electron microscopy showed adherence of H. pylori organisms to epithelial cell surface. In six animals, intracytoplasmic location of this bacterium was observed in the antrum or the fundus. These results allow us to propose this model as a new ex vivo model for the study of specific H. pylori-gastric cell interactions.


* Corresponding author. Mailing address: Laboratoire de Bactériologie, Hôpital Central, 29 Avenue du Maréchal de Lattre de Tassigny, 54035 Nancy Cedex, France. Phone: (33) 3 83 85 21 96. Fax: (33) 3 83 85 26 73. E-mail: a.lozniewski{at}chu-nancy.fr.


Infection and Immunity, April 1999, p. 1798-1805, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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