Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host.
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 beta-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.
Barthel
Manja
M
Institute of Microbiology, ETH Zürich, 8092 Zürich, Switzerland.
Hapfelmeier
Siegfried
S
Quintanilla-Martínez
Leticia
L
Kremer
Marcus
M
Rohde
Manfred
M
Hogardt
Michael
M
Pfeffer
Klaus
K
Rüssmann
Holger
H
Hardt
Wolf-Dietrich
WD
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007778:Lactobacillus / Q000472:pathogenicity; D008221:Lymphoid Tissue / Q000276:immunology; D053259:Lymphotoxin beta Receptor; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D012481:Salmonella Infections, Animal / Q000209:etiology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D013307:Streptomycin / Q000494:pharmacology*
D001426:Bacterial Proteins; C505697:LTBR protein, human; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D018124:Receptors, Tumor Necrosis Factor; D013307:Streptomycin