title: Activation of innate immune genes in caprine blood leukocytes after systemic endotoxin challenge.
abstract: BACKGROUND
  Sepsis is a serious health problem associated with a range of infectious diseases in animals and humans. Early events of this syndrome can be mimicked by experimental administration of lipopolysaccharides (LPS). Compared with mice, small ruminants and humans are highly sensitive to LPS, making goats valuable in inflammatory models. We performed a longitudinal study in eight Norwegian dairy goats that received LPS (0.1 μg/kg, Escherichia coli O26:B6) intravenously. A control group of five goats received corresponding volumes of sterile saline. Clinical examinations were performed continuously, and blood samples were collected throughout the trial.
  
  
  RESULTS
  Characteristic signs of acute sepsis, such as sickness behavior, fever, and leukopenia were observed within 1 h of LPS administration. A high-throughput longitudinal gene expression analysis of circulating leukocytes was performed, and genes associated with the acute phase response, type I interferon signaling, LPS cascade and apoptosis, in addition to cytokines and chemokines were targeted. Pro-inflammatory genes, such as IL1B, CCL3 and IL8, were significantly up-regulated. Interestingly, increased mRNA levels of seven interferon stimulated genes (ISGs) were observed peaking at 2 h, corroborating the increasing evidence that ISGs respond immediately to bacterial endotoxins. A slower response was manifested by four extrahepatic acute phase proteins (APP) (SAA3, HP, LF and LCN2) reaching maximum levels at 5 h.
  
  
  CONCLUSIONS
  We report an immediate induction of ISGs in leukocytes in response to LPS supporting a link between the interferon system and defense against bacterial infections. The extrahepatic expression of APPs suggests that leukocytes contribute to synthesis of these proteins at the beginning of a systemic inflammation. Taken together, these findings provide insights into the dynamic regulation of innate immune genes, as well as raising new questions regarding the importance of ISGs and extrahepatic APPs in leukocytes after systemic endotoxin challenge.
authors: Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.
authors: Øyvind
authors: Ø
authors: Salvesen
authors: Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.
authors: Malin R
authors: MR
authors: Reiten
authors: Innate Immunology Group, Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
authors: Peter M H
authors: PM
authors: Heegaard
authors: Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.
authors: Michael A
authors: MA
authors: Tranulis
authors: Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.
authors: Arild
authors: A
authors: Espenes
authors: Innate Immunology Group, Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
authors: Kerstin
authors: K
authors: Skovgaard
authors: Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway. cecilie.ersdal@nmbu.no.
authors: Cecilie
authors: C
authors: Ersdal
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000276:immunology*; D005260:Female; D006041:Goats; D007113:Immunity, Innate / Q000235:genetics*; D007372:Interferons / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*
chemical_list: D004731:Endotoxins; D007372:Interferons
keywords: Blood leukocyte gene expression; Endotoxemia; Extrahepatic acute phase proteins; Goat; Innate immunity; Interferon stimulated genes; Lipopolysaccharide (LPS); Systemic inflammation