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Immune gene expression profiling of Proliferative Kidney Disease in rainbow trout Oncorhynchus mykiss reveals a dominance of anti-inflammatory, antibody and T helper cell-like activities.

Gorgoglione B, Wang T, Secombes CJ, Holland JW - Vet. Res. (2013)

Bottom Line: The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology.Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease.Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets.

View Article: PubMed Central - HTML - PubMed

Affiliation: Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, UK. j.holland@abdn.ac.uk.

ABSTRACT
The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology. Although known to be associated with suppression of some cellular aspects of innate immunity and a prominent lymphocytic hyperplasia, there remains a considerable knowledge gap in our understanding of the underlying immune mechanisms driving PKD pathogenesis. To provide further insights, the expression profiles of a panel of innate/inflammatory and adaptive immune molecules were examined in rainbow trout Oncorhynchus mykiss following a natural exposure to the parasite. Relative to controls, fish with early to advanced stages of kidney pathology exhibited up-regulation of the inflammatory cytokines interleukin (IL)-6 and IL-11, although remaining refractory towards genes indicative of macrophage activity. Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease. Up-regulation of adaptive immune molecules, including cell markers and antibody genes reflect the lymphocytic dominance of this disease and the likely importance of lymphocyte subsets in PKD pathogenesis. Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets. This work, for the first time in the study of fish-myxozoan interactions, suggests that PKD pathogenesis is shaped by an anti-inflammatory phenotype, a profound B cell/antibody response and dysregulated TH cell-like activities. A better understanding of the functional roles of fish immune cells and molecules in PKD pathogenesis may facilitate future development of control measures against this disease.

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Correlation of T. bryosalmonae prevalence and cell/antibody marker genes in rainbow trout kidney. (A) CD8α; (B) CD8ß; (C) IL-2Rß; (D) secretory IgD; (E) secretory IgM; (F) secretory IgT. Pearson correlation r coefficients are given relative to T. bryosalmonae RPL18 and kidney swelling (in parentheses). Significant correlations are shown in bold. *P < 0.05; **P < 0.01 (2-tailed).
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Figure 5: Correlation of T. bryosalmonae prevalence and cell/antibody marker genes in rainbow trout kidney. (A) CD8α; (B) CD8ß; (C) IL-2Rß; (D) secretory IgD; (E) secretory IgM; (F) secretory IgT. Pearson correlation r coefficients are given relative to T. bryosalmonae RPL18 and kidney swelling (in parentheses). Significant correlations are shown in bold. *P < 0.05; **P < 0.01 (2-tailed).

Mentions: Overall, 36 gene transcripts correlated positively with parasite RPL18 transcript levels, with 9 genes (IL-6, IL-10A, IL-21, IgT (secretory), interferon (IFN) γ, suppressor of cytokine signalling (SOCS)-3, CATH-1, CATH-2 & hepcidin-1) strongly correlated (r ≥ 0.7) (Figures 2, 3, 4, 5, 6, 7 and 8. See Additional file 2 for IL-18, IgT (membrane), type I IFN-A, IL-10B, SOCS-1, and IL-15 data). Sixteen genes correlated positively with both parasite RPL18 and kidney swelling, including all genes strongly correlating with RPL18, together with IL-10B, IL-11, MCSF-1, arginase-1, IgM (secretory), IgT (membrane) and SOCS-1. Conversely, four genes correlated with the kidney swelling grade and not parasite RPL18, namely; MCSF-R1, RAR-related orphan receptor (ROR)γ, IL-17C-2 and SOCS-2 (Figures 3 and 7. See Additional file 2 for RORγ and SOCS-2 data). In each case a weak negative correlation was evident. Below, we focus on those genes correlating with parasite RPL18 expression, 55.6% (20 genes) of which would not have been detected by examining potential correlations between immune gene expression and kidney swelling grade alone.


Immune gene expression profiling of Proliferative Kidney Disease in rainbow trout Oncorhynchus mykiss reveals a dominance of anti-inflammatory, antibody and T helper cell-like activities.

Gorgoglione B, Wang T, Secombes CJ, Holland JW - Vet. Res. (2013)

Correlation of T. bryosalmonae prevalence and cell/antibody marker genes in rainbow trout kidney. (A) CD8α; (B) CD8ß; (C) IL-2Rß; (D) secretory IgD; (E) secretory IgM; (F) secretory IgT. Pearson correlation r coefficients are given relative to T. bryosalmonae RPL18 and kidney swelling (in parentheses). Significant correlations are shown in bold. *P < 0.05; **P < 0.01 (2-tailed).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3733943&req=5

Figure 5: Correlation of T. bryosalmonae prevalence and cell/antibody marker genes in rainbow trout kidney. (A) CD8α; (B) CD8ß; (C) IL-2Rß; (D) secretory IgD; (E) secretory IgM; (F) secretory IgT. Pearson correlation r coefficients are given relative to T. bryosalmonae RPL18 and kidney swelling (in parentheses). Significant correlations are shown in bold. *P < 0.05; **P < 0.01 (2-tailed).
Mentions: Overall, 36 gene transcripts correlated positively with parasite RPL18 transcript levels, with 9 genes (IL-6, IL-10A, IL-21, IgT (secretory), interferon (IFN) γ, suppressor of cytokine signalling (SOCS)-3, CATH-1, CATH-2 & hepcidin-1) strongly correlated (r ≥ 0.7) (Figures 2, 3, 4, 5, 6, 7 and 8. See Additional file 2 for IL-18, IgT (membrane), type I IFN-A, IL-10B, SOCS-1, and IL-15 data). Sixteen genes correlated positively with both parasite RPL18 and kidney swelling, including all genes strongly correlating with RPL18, together with IL-10B, IL-11, MCSF-1, arginase-1, IgM (secretory), IgT (membrane) and SOCS-1. Conversely, four genes correlated with the kidney swelling grade and not parasite RPL18, namely; MCSF-R1, RAR-related orphan receptor (ROR)γ, IL-17C-2 and SOCS-2 (Figures 3 and 7. See Additional file 2 for RORγ and SOCS-2 data). In each case a weak negative correlation was evident. Below, we focus on those genes correlating with parasite RPL18 expression, 55.6% (20 genes) of which would not have been detected by examining potential correlations between immune gene expression and kidney swelling grade alone.

Bottom Line: The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology.Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease.Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets.

View Article: PubMed Central - HTML - PubMed

Affiliation: Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, UK. j.holland@abdn.ac.uk.

ABSTRACT
The myxozoan Tetracapsuloides bryosalmonae is the causative agent of Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected fish where it causes a chronic lymphoid immunopathology. Although known to be associated with suppression of some cellular aspects of innate immunity and a prominent lymphocytic hyperplasia, there remains a considerable knowledge gap in our understanding of the underlying immune mechanisms driving PKD pathogenesis. To provide further insights, the expression profiles of a panel of innate/inflammatory and adaptive immune molecules were examined in rainbow trout Oncorhynchus mykiss following a natural exposure to the parasite. Relative to controls, fish with early to advanced stages of kidney pathology exhibited up-regulation of the inflammatory cytokines interleukin (IL)-6 and IL-11, although remaining refractory towards genes indicative of macrophage activity. Antimicrobial peptides (AMPs) and anti-inflammatory markers, including cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease. Up-regulation of adaptive immune molecules, including cell markers and antibody genes reflect the lymphocytic dominance of this disease and the likely importance of lymphocyte subsets in PKD pathogenesis. Up-regulation of T helper (TH) cell-like response genes and transcription factors implies that T. bryosalmonae may elicit a complex interplay between TH cell subsets. This work, for the first time in the study of fish-myxozoan interactions, suggests that PKD pathogenesis is shaped by an anti-inflammatory phenotype, a profound B cell/antibody response and dysregulated TH cell-like activities. A better understanding of the functional roles of fish immune cells and molecules in PKD pathogenesis may facilitate future development of control measures against this disease.

Show MeSH
Related in: MedlinePlus