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.

Highlights

  • Proliferative Kidney Disease of salmonid fish is a slow progressive disease of major economic importance to aquaculture in the UK, Mainland Europe, and the USA [1,2]

  • Pathogen detection Trout exposed to parasite-infected water were found to exhibit a range of clinical pathology ranging from grade 1 at low levels to grade 3 in cases of severe/advanced kidney pathology. 18S rDNA levels steadily increased in kidney tissue samples from grade 1 to grade 3 fish, reaching maximal levels in grade 3 fish whilst remaining undetectable in uninfected fish (Figure 1A)

  • Agar plates prepared from kidney swabs from uninfected and T. bryosalmonae infected fish did not reveal the presence of bacterial pathogens, implying that the immune gene expression profiles observed in this study are influenced by the presence of T. bryosalmonae

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Summary

Introduction

Proliferative Kidney Disease of salmonid fish is a slow progressive disease of major economic importance to aquaculture in the UK, Mainland Europe, and the USA [1,2]. Extrasporogonic proliferation in the kidney interstitium provokes a chronic immunopathology characterized by a lymphocytic hyperplasia, formation of granulomatous lesions, renal atrophy, and hyper secretion of immunoglobulins [1,2] These stages are eventually eliminated in surviving fish and normal kidney function restored. In the absence of effective control measures immune therapy may be a way forward This will necessitate an in-depth understanding of the immune mechanisms underlying the kidney immunopathology and protective immune responses to PKD. This is poignant given that fish surviving PKD are immune to re-infection, providing the necessary impetus for vaccine development [1]

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