Role of neutrophils in murine salmonellosis.
Gastrointestinal infections with Salmonella enterica serovars have different clinical outcomes that range from localized inflammation to a life-threatening systemic disease in the case of typhoid fever. Using a mouse model of systemic salmonellosis, we investigated the contribution of neutrophils to the innate immune defense against Salmonella after oral infection. Neutrophil infiltration was dependent on the bacterial burden in various infected organs (Peyer's patches, mesenteric lymph nodes, spleen, and liver). However, the massive infiltration of neutrophils did not allow clearance of an infection with wild-type Salmonella, presumably due to protection of intracellular Salmonella against neutrophil activities. A Salmonella mutant strain deficient in Salmonella pathogenicity island 2 (SPI2) was able to infect systemic sites, but its replication was highly restricted and it did not cause detectable attraction of neutrophils. Neutrophil depletion by antibody treatment of mice did not restore the virulence of SPI2 or auxotrophic mutant strains, supporting the hypothesis that attenuation of the strains is not due to greater susceptibility to neutrophil killing. Our observations reveal that neutrophils have completely different roles during systemic salmonellosis and localized gastrointestinal infections. In the latter conditions, rapid neutrophil attraction efficiently prevents the spread of the pathogen, whereas the neutrophil influx is delayed during systemic infections and cannot protect against lethal bacteremia.
Cheminay
Cédric
C
Institut für Klinische Mikrobiologie, Immunologie und Hygiene, FAU Erlangen-Nürnberg, D-91054 Erlangen, Germany.
Chakravortty
Dipshikha
D
Hensel
Michael
M
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009503:Neutropenia; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology*; D009928:Organ Specificity; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics
D001426:Bacterial Proteins; D008565:Membrane Proteins; C440638:SPI-2 protein, Salmonella; D037521:Virulence Factors