High gene expression of inflammatory markers and IL-17A correlates with severity of injection site reactions of Atlantic salmon vaccinated with oil-adjuvanted vaccines
Date
2010-05-27
Authors
Mutoloki, Stephen
Cooper, Glenn A.
Marjara, Inderjit S.
Koop, Benjamin F.
Evensen, Øystein
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
Background: Two decades after the introduction of oil-based vaccines in the control of bacterial and viral diseases in
farmed salmonids, the mechanisms of induced side effects manifested as intra-abdominal granulomas remain
unresolved. Side effects have been associated with generation of auto-antibodies and autoimmunity but the
underlying profile of inflammatory and immune response has not been characterized. This study was undertaken with
the aim to elucidate the inflammatory and immune mechanisms of granuloma formation at gene expression level
associated with high and low side effect (granuloma) indices.
Groups of Atlantic salmon parr were injected intraperitoneally with oil-adjuvanted vaccines containing either high or
low concentrations of Aeromonas salmonicida or Moritella viscosa antigens in order to induce polarized (severe and
mild) granulomatous reactions. The established granulomatous reactions were confirmed by gross and histological
methods at 3 months post vaccination when responses were known to have matured. The corresponding gene
expression patterns in the head kidneys were profiled using salmonid cDNA microarrays followed by validation by realtime
quantitative PCR (qPCR). qPCR was also used to examine the expression of additional genes known to be
important in the adaptive immune response.
Results: Granulomatous lesions were observed in all vaccinated fish. The presence of severe granulomas was
associated with a profile of up-regulation of innate immunity-related genes such as complement factors C1q and C6,
mannose binding protein, lysozyme C, C-type lectin receptor, CD209, Cathepsin D, CD63, LECT-2, CC chemokine and
metallothionein. In addition, TGF-β (p = 0.001), IL-17A (p = 0.007) and its receptor (IL-17AR) (p = 0.009) representing
TH17 were significantly up-regulated in the group with severe granulomas as were arginase and IgM. None of the
genes directly reflective of TH1 T cell lineage (IFN-γ, CD4) or TH2 (GATA-3) responses were differentially expressed.
Conclusions: Granulomatous reactions following vaccination with oil-based vaccines in Atlantic salmon have the
profile of strong expression of genes related to innate immune responses. The expression of TGF-β, IL-17A and its
receptor suggests an involvement of TH17 T cell lineage and is in conformity with strong infiltration of neutrophils and
macrophages into inflamed areas. Arginase upregulation shows that macrophages in these reactions are alternatively
activated, indicating also a TH2-profile. To what extent the expression of IL-17A and its receptor reflects an autoimmune
vaccine-based reaction remains elusive but would be in conformity with previous observations of autoimmune
reactions in salmon when vaccinated with oil-based vaccines.
Description
BioMed Central
Keywords
Citation
Mutoloki et al., High gene expression of inflammatory markers and IL-17A correlates with severity of injection site reactions of Atlantic salmon vaccinated with oil-adjuvanted vaccines BMC Genomics 2010, 11:336