title: Increased resistance against acute polymicrobial sepsis in mice challenged with immunostimulatory CpG oligodeoxynucleotides is related to an enhanced innate effector cell response.
abstract: Recent reports support the concept that the major defect in polymicrobial sepsis is an impaired immunologic response to infection. Oligodeoxynucleotides containing CpG sequence motifs (CpG-ODN) were previously shown to induce immune protection in models of chronic infection with intracellular bacteria, parasites, and viruses due to their ability to augment IFN-gamma-dependent Th1 responses. Here, we demonstrate that challenging mice with CpG-ODN substantially increases the resistance against acute polymicrobial sepsis. Systemic levels of IL-12, IL-18, and IL-10 were not altered in CpG-ODN-treated mice as compared with controls. In contrast, administration of CpG-ODN resulted in a strongly enhanced accumulation of neutrophils at the primary site of infection. Neutrophils of CpG-ODN-treated mice exhibited an up-regulation of phagocytic receptors, an increased phagocytic activity, and an elevated production of reactive oxygen metabolites. These results suggest that the protective effects of CpG-ODNs in acute polymicrobial sepsis are related to an enhanced effector cell response of innate immunity. CpG-ODN may therefore represent potent agents for the treatment of sepsis-associated immunoparalysis.
authors.affiliation: Department of Surgery, Klinikum rechts der Isar, and Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität, Munich, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Weighardt
authors.forename: C
authors.initials: C
authors.lastname: Feterowski
authors.forename: M
authors.initials: M
authors.lastname: Veit
authors.forename: M
authors.initials: M
authors.lastname: Rump
authors.forename: H
authors.initials: H
authors.lastname: Wagner
authors.forename: B
authors.initials: B
authors.lastname: Holzmann
mesh_terms: D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology*; D010538:Peritonitis / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control; D010587:Phagocytosis / Q000276:immunology; D016897:Respiratory Burst / Q000276:immunology; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology* / Q000401:mortality / Q000517:prevention & control; D016019:Survival Analysis
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides