title: Hepatic gene expression profiling reveals protective responses in Atlantic salmon vaccinated against furunculosis.
abstract: BACKGROUND
  Furunculosis, a disease caused with gram negative bacteria Aeromonas salmonicida produces heavy losses in aquaculture. Vaccination against furunculosis reduces mortality of Atlantic salmon but fails to eradicate infection. Factors that determine high individual variation of vaccination efficiency remain unknown. We used gene expression analyses to search for the correlates of vaccine protection against furunculosis in Atlantic salmon.
  
  
  RESULTS
  Naïve and vaccinated fish were challenged by co-habitance. Fish with symptoms of furunculosis at the onset of mass mortality (LR - low resistance) and survivors (HR - high resistance) were sampled. Hepatic gene expression was analyzed with microarray (SFA2.0 - immunochip) and real-time qPCR. Comparison of LR and HR indicated changes associated with the protection and results obtained with naïve fish were used to find and filter the vaccine-independent responses. Genes involved in recruitment and migration of immune cells changed expression in both directions with greater magnitude in LR. Induction of the regulators of immune responses was either equal (NFkB) or greater (Jun) in LR. Expression levels of proteasome components and extracellular proteases were higher in LR while protease inhibitors were up-regulated in HR. Differences in chaperones and protein adaptors, scavengers of reactive oxygen species and genes for proteins of iron metabolism suggested cellular and oxidative stress in LR. Reduced levels of free iron and heme can be predicted in LR by gene expression profiles with no protection against pathogen. The level of complement regulation was greater in HR, which showed up-regulation of the components of membrane attack complex and the complement proteins that protect the host against the auto-immune damages. HR fish was also characterized with up-regulation of genes for proteins involved in the protection of extracellular matrix, lipid metabolism and clearance of endogenous and exogenous toxic compounds. A number of genes with marked expression difference between HR and LR can be considered as positive and negative correlates of vaccine protection against furunculosis.
  
  
  CONCLUSIONS
  Efficiency of vaccination against furunculosis depends largely on the ability of host to neutralize the negative impacts of immune responses combined with efficient clearance and prevention of tissue damages.
authors.affiliation: Nofima Marin, As 1430, Norway. Stanko.Skugor@nofima.no
authors.forename: Stanko
authors.initials: S
authors.lastname: Skugor
authors.forename: Sven Martin
authors.initials: SM
authors.lastname: Jørgensen
authors.forename: Bjarne
authors.initials: B
authors.lastname: Gjerde
authors.forename: Aleksei
authors.initials: A
authors.lastname: Krasnov
mesh_terms: D048409:Aeromonas salmonicida / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D005667:Furunculosis / Q000276:immunology / Q000517:prevention & control*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology; D020317:Salmo salar / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D014611:Vaccination
chemical_list: D000900:Anti-Bacterial Agents; D003165:Complement System Proteins; D007501:Iron