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Infection and Immunity, September 2006, p. 5047-5057, Vol. 74, No. 9
0019-9567/06/$08.00+0     doi:10.1128/IAI.00072-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Chronic Salmonella enterica Serovar Typhimurium-Induced Colitis and Cholangitis in Streptomycin-Pretreated Nramp1+/+ Mice

Bärbel Stecher,1,{dagger} Günther Paesold,1,{dagger},{ddagger} Manja Barthel,1 Marcus Kremer,2 Jonathan Jantsch,3 Thomas Stallmach,3 Mathias Heikenwalder,4 and Wolf-Dietrich Hardt1*

Institute of Microbiology, D-BIOL, ETH Zürich, Wolfgang-Pauli Strasse 10, 8093 Zürich,1 Institute of Clinical Pathology,3 Institute of Neuropathology, Universitätsspital Zürich, Schmelzbergstrasse 12, 8091 Zürich, Switzerland,4 Institute of Pathology, Technische Universität München, Ismaninger Strasse 22, D-81675 Munich, Germany2

Received 13 January 2006/ Returned for modification 17 February 2006/ Accepted 13 June 2006

Salmonella enterica subspecies 1 serovar Typhimurium is an enteric bacterial pathogen infecting a broad range of hosts. In susceptible Nramp1–/– (Slc11{alpha}1–/–) mice, serovar Typhimurium cannot efficiently colonize the intestine but causes a systemic typhoid-like infection. However, after pretreatment with streptomycin, these susceptible (C57BL/6 and BALB/c) mice develop acute serovar Typhimurium-induced colitis (M. Barthel et al., Infect. Immun. 71:2839-2858, 2003). It was not clear whether resistant Nramp1+/+ (Slc11{alpha}1+/+) mouse strains would similarly develop colitis. Here we compared serovar Typhimurium infection in streptomycin-pretreated susceptible (C57BL/6) and resistant (DBA/2 and 129Sv/Ev) mouse strains: We found that acute colitis (days 1 and 3 postinfection) is strikingly similar in susceptible and resistant mice. In 129Sv/Ev mice we followed the serovar Typhimurium infection for as long as 6 weeks. After the initial phase of acute colitis, these animals developed chronic crypt-destructive colitis, including ulceration, crypt abscesses, pronounced mucosal and submucosal infiltrates, overshooting regeneration of the epithelium, and crypt branching. Moreover, we observed inflammation of the gall duct epithelium (cholangitis) in the 129Sv/Ev mice between days 14 and 43 of infection. Cholangitis was not attributable to side effects of the streptomycin treatment. Furthermore, chronic infection of 129Sv/Ev mice in a typhoid fever model did not lead to cholangitis. We propose that streptomycin-pretreated 129Sv/Ev mice provide a robust murine model for chronic enteric salmonellosis including complications such as cholangitis.

* Corresponding author. Mailing address: Institute of Microbiology, ETH Zürich, Wolfgang-Pauli Strasse 10, 8093 Zürich, Switzerland. Phone: 01-632-5143. Fax: 01-632-1129. E-mail: hardt{at}micro.biol.ethz.ch.

Editor: J. B. Bliska

{dagger} B.S. and G.P. contributed equally to this work.

{ddagger} Present address: Universitätsklinik Balgrist, Forchstrasse 340, 8008 Zürich, Switzerland.

Infection and Immunity, September 2006, p. 5047-5057, Vol. 74, No. 9
0019-9567/06/$08.00+0     doi:10.1128/IAI.00072-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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