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Infection and Immunity, May 2003, p. 2839-2858, Vol. 71, No. 5
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.5.2839-2858.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Pretreatment of Mice with Streptomycin Provides a Salmonella enterica Serovar Typhimurium Colitis Model That Allows Analysis of Both Pathogen and Host
Manja Barthel,1,2 Siegfried Hapfelmeier,1,2 Leticia Quintanilla-Martínez,3 Marcus Kremer,3,4 Manfred Rohde,5 Michael Hogardt,2 Klaus Pfeffer,6 Holger Rüssmann,2 and Wolf-Dietrich Hardt1*
Institute of Microbiology, ETH Zürich, 8092 Zürich, Switzerland,1
Max von Pettenkofer-Institut, Ludwig Maximilians Universität, 80336 Munich,2
Institute of Medical Microbiology, Immunology, and Hygiene,4
Institute of Pathology, Technical University of Munich, 81675 Munich,6
GSF-Research Center for Environment and Health, 85764 Neuherberg,3
GBF, 38124 Braunschweig, Germany5
Received 25 November 2002/
Returned for modification 16 January 2003/
Accepted 6 February 2003
Salmonella enterica subspecies 1 serovar Typhimurium is a principal cause of human enterocolitis. For unknown reasons, in mice serovar Typhimurium does not provoke intestinal inflammation but rather targets the gut-associated lymphatic tissues and causes a systemic typhoid-like infection. The lack of a suitable murine model has limited the analysis of the pathogenetic mechanisms of intestinal salmonellosis. We describe here how streptomycin-pretreated mice provide a mouse model for serovar Typhimurium colitis. Serovar Typhimurium colitis in streptomycin-pretreated mice resembles many aspects of the human infection, including epithelial ulceration, edema, induction of intercellular adhesion molecule 1, and massive infiltration of PMN/CD18+ cells. This pathology is strongly dependent on protein translocation via the serovar Typhimurium SPI1 type III secretion system. Using a lymphotoxin ß-receptor knockout mouse strain that lacks all lymph nodes and organized gut-associated lymphatic tissues, we demonstrate that Peyer's patches and mesenteric lymph nodes are dispensable for the initiation of murine serovar Typhimurium colitis. Our results demonstrate that streptomycin-pretreated mice offer a unique infection model that allows for the first time to use mutants of both the pathogen and the host to study the molecular mechanisms of enteric salmonellosis.
* Corresponding author. Mailing address: Institute of Microbiology, ETH Zürich, Schmelzbergstr. 7, 8092 Zürich, Switzerland. Phone: 41-1-632-5143. Fax: 41-1-632-1129. E-mail:
hardt{at}micro.biol.ethz.ch.
Editor: D. L. Burns
Infection and Immunity, May 2003, p. 2839-2858, Vol. 71, No. 5
0019-9567/03/$08.00+0 DOI: 10.1128/IAI.71.5.2839-2858.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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