title: The importance of a lipopolysaccharide-initiated, cytokine-mediated host defense mechanism in mice against extraintestinally invasive Escherichia coli.
abstract: Extraintestinally invasive Escherichia coli (EC) that possess both a complete LPS and K1 capsule evade both complement-mediated bacteriolysis and neutrophil-mediated killing. Since C3H/HeJ mice that are hyporesponsive to LPS were uniquely susceptible to lethal infection with EC of this phenotype, we speculated there was an LPS-initiated host defense mechanism against this pathogenic phenotype. The LPS-normoresponsive C3H/HeN as well as the C3H/HeJ mice cleared these EC from the circulation within 4 h of intravenous administration. Whereas electron micrographs of the liver demonstrated these EC undergoing degeneration within the phagolysosomes of of both macrophages and Kupffer cells of C3H/HeN mice, these EC replicated within these cells of the C3H/HeJ mice. Restoration of anti-EC activity of C3H/HeJ mice occurred with activation of Kupffer cells and peritoneal macrophages in vivo with BCG and in vitro with IFN-gamma, but not with LPS. Pretreatment of C3H/HeJ mice with a combination of recombinant murine IL-1 and TNF-alpha also restored the killing of K1(+)-EC but did not enhance the killing of a K1(-)-EC mutant. These data are consistent with the hypothesis that (a) there is no intrinsic inability of C3H/HeJ phagocytes to kill EC, but (b) an LPS-initiated, cytokine-mediated host defense mechanism is required for such killing. These studies emphasize the importance of bacterial surface characteristics in the interaction with specific host defenses.
authors.affiliation: Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
authors.forename: A
authors.initials: A
authors.lastname: Cross
authors.forename: L
authors.initials: L
authors.lastname: Asher
authors.forename: M
authors.initials: M
authors.lastname: Seguin
authors.forename: L
authors.initials: L
authors.lastname: Yuan
authors.forename: N
authors.initials: N
authors.lastname: Kelly
authors.forename: C
authors.initials: C
authors.lastname: Hammack
authors.forename: J
authors.initials: J
authors.lastname: Sadoff
authors.forename: P
authors.initials: P
authors.lastname: Gemski
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D016470:Bacteremia / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D016667:Bacterial Capsules; D001433:Bacteriolysis; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D005260:Female; D020022:Genetic Predisposition to Disease; D007155:Immunologic Factors / Q000627:therapeutic use; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology / Q000627:therapeutic use; D007728:Kupffer Cells / Q000502:physiology / Q000648:ultrastructure; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000633:toxicity*; D008247:Lysosomes / Q000502:physiology; D008262:Macrophage Activation / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000502:physiology; D009895:Opsonin Proteins / Q000276:immunology; D010538:Peritonitis / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control; D010587:Phagocytosis; D011135:Polysaccharides, Bacterial / Q000502:physiology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D000954:Antigens, Surface; D016207:Cytokines; D004731:Endotoxins; D007155:Immunologic Factors; D007375:Interleukin-1; C030659:K antigens; D008070:Lipopolysaccharides; D009895:Opsonin Proteins; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C036962:capsular polysaccharide K1; C044101:endotoxin, Escherichia coli; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma