title: Neutrophil influx in response to a peritoneal infection with Salmonella is delayed in lipopolysaccharide-binding protein or CD14-deficient mice.
abstract: The induction of an adaptive immune response to a previously unencountered pathogen is a time-consuming process and initially the infection must be held in check by the innate immune system. In the case of an i.p. infection with Salmonella typhimurium, survival requires both CD14 and LPS-binding protein (LBP) which, together with Toll-like receptor 4 and myeloid differentiation protein 2, provide a sensitive means to detect bacterial LPS. In this study, we show that in the first hours after i.p. infection with Salmonella a local inflammatory response is evident and that concomitantly neutrophils flood into the peritoneum. This rapid neutrophil influx is dependent on TNF since it is 1) abolished in TNF KO mice and 2) can be induced by i.p. injection of TNF in uninfected animals. Neutrophil influx is not strictly dependent on the presence of either LBP or CD14. However, in their absence, no local inflammatory response is evident, neutrophil migration is delayed, and the mice succumb to the infection. Using confocal microscopy, we show that the neutrophils which accumulate in CD14 and LBP null mice, albeit with delayed kinetics, are nevertheless fully capable of ingesting the bacteria. We suggest that the short delay in neutrophil influx gives the pathogen a decisive advantage in this infection model.
authors.affiliation: Department of Immunology, Klinikum der Universität Greifswald, Sauerbruchstrasse, D-17489 Greifswald, Germany.
authors.forename: Kang K
authors.initials: KK
authors.lastname: Yang
authors.forename: Brigitte G
authors.initials: BG
authors.lastname: Dorner
authors.forename: Ulrike
authors.initials: U
authors.lastname: Merkel
authors.forename: Bernard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Christine
authors.initials: C
authors.lastname: Schütt
authors.forename: Douglas
authors.initials: D
authors.lastname: Golenbock
authors.forename: Mason W
authors.initials: MW
authors.lastname: Freeman
authors.forename: Robert S
authors.initials: RS
authors.lastname: Jack
mesh_terms: D000209:Acute-Phase Proteins; D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D010538:Peritonitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000032:analysis / Q000172:deficiency / Q000235:genetics; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein