Abstract
BackgroundIn mammalian vertebrates, the cytokine interleukin (IL)-12 consists of a heterodimer between p35 and p40 subunits whereas interleukin-23 is formed by a heterodimer between p19 and p40 subunits. During an immune response, the balance between IL-12 and IL-23 can depend on the nature of the pathogen associated molecular pattern (PAMP) recognized by, for example TLR2, leading to a preferential production of IL-23. IL-23 production promotes a Th17-mediated immune response characterized by the production of IL-17A/F and several chemokines, important for neutrophil recruitment and activation. For the cold blooded vertebrate common carp, only the IL-12 subunits have been described so far.Methodology/Principal FindingsCommon carp is the natural host of two protozoan parasites: Trypanoplasma borreli and Trypanosoma carassii. We found that these parasites negatively affect p35 and p40a gene expression in carp. Transfection studies of HEK293 and carp macrophages show that T. carassii-derived PAMPs are agonists of carp TLR2, promoting p19 and p40c gene expression. The two protozoan parasites induce different immune responses as assessed by gene expression and histological studies. During T. carassii infections, in particular, we observed a propensity to induce p19 and p40c gene expression, suggestive of the formation of IL-23. Infections with T. borreli and T. carassii lead to an increase of IFN-γ2 gene expression whereas IL-17A/F2 gene expression was only observed during T. carasssii infections. The moderate increase in the number of splenic macrophages during T. borreli infection contrasts the marked increase in the number of splenic neutrophilic granulocytes during T. carassii infection, along with an increased gene expression of metalloproteinase-9 and chemokines.Conclusion/SignificanceThis is the first study that provides evidence for a Th17-like immune response in fish in response to infection with a protozoan parasite.
Highlights
In mammalian vertebrates, the three members of the IL-12 cytokine family comprise the heterodimeric IL-12, IL-23 and IL27; all molecules belonging to the type I cytokine superfamily
The supernatant was used to study the possibility that GPI-anchored proteins from T. borreli and T. carassii can act as pathogen associated molecular pattern (PAMP) of carp TLR2
Activated macrophages are antagonized by type 2 anti-inflammatory responses, which are driven by the development of alternatively activated macrophages
Summary
The three members of the IL-12 cytokine family comprise the heterodimeric IL-12, IL-23 and IL27; all molecules belonging to the type I cytokine superfamily. IL12 consists of two disulphide-linked proteins: the p35 and the p40 subunit, together forming IL-12p70 [1]. The last member of the family, IL-27, consists of a heterodimer between two other subunits, both with homology to the p35 and p40 subunits, respectively, named p28 and EBI3 [3]. The cytokine interleukin (IL)-12 consists of a heterodimer between p35 and p40 subunits whereas interleukin-23 is formed by a heterodimer between p19 and p40 subunits. The balance between IL-12 and IL-23 can depend on the nature of the pathogen associated molecular pattern (PAMP) recognized by, for example TLR2, leading to a preferential production of IL-23. IL-23 production promotes a Th17-mediated immune response characterized by the production of IL-17A/F and several chemokines, important for neutrophil recruitment and activation. For the cold blooded vertebrate common carp, only the IL-12 subunits have been described so far
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