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The aetiology of amoebic gill disease (AGD) and aspects of the host immune response to infection
thesisposted on 2023-05-26, 04:17 authored by Young, ND
Amoebic gill disease (AGD) is an ectoparasitic condition of some marine fish. Atlantic salmon are highly susceptible to AGD and the cost of mitigation is a significant financial burden for the aquaculture industry, particularly in Tasmania, Australia. Despite a considerable research effort over the past 20 years, two fundamental questions remain unanswered: 1. Which species of amoeba causes AGD? Two species of amoebae, Neoparamoeba pemaquidensis and Neoparamoeba branchiphila have been isolated from the gills of AGD-affected fish. Based on morphology alone, either species may be associated with AGD yet all attempts to experimentally induce AGD with cultured strains of either species have been unsuccessful. 2. Why are Atlantic salmon highly susceptible to AGD and is this susceptibility linked to aberrant innate and adaptive immune responses? In this thesis, the aetiology of AGD was resolved by identifying and characterising a new species of amoeba, Neoparamoeba perurans and demonstrating that this species is the only known aetiological agent of AGD globally. In so doing, the phylogeny of Neoparamoeba was resolved and the strict co-evolution of Neoparamoeba species with their endosymbiont, Perkinsela amoebae-like organism was confirmed as a defining characteristic amongst all members of the Neoparamoeba. Following this, the mechanisms that underpin the susceptibility of Atlantic salmon to AGD were assessed. Global gene expression profiling the gills of AGD-affected fish revealed that transcripts associated with the immune response were almost universally down-regulated in AGD-lesions specifically. In AGD-affected tissue, significant, coordinated down-regulation of the major histocompatibility complex class I (MHC I), and possibly the MHC II pathway-related genes occurred during the later stages of infection and appeared to be mediated by down-regulation of interferon-regulatory factor (IRF)-1, independent of interferon-‚àö¬8, interferon-y (IFN- ‚àö¬£) and IRF-2 expression. Stimulating AGD-lesions ex vivo with recombinant IFN-y failed to restore the expression of IRF-1 and the MHC I receptor molecule, thus confirming earlier observations that the MHC I antigen presentation pathway appears to be modulated independently of IFN-y in AGD lesions. Within the AGD lesion microenvironment, suppression of the MHC I and possibly the MHC II pathways may inhibit the development of acquired immunity and could explain the unusually high susceptibility of Atlantic salmon to AGD. Whilst the data are preliminary, the immunologically unresponsiveness of the AGD lesion microenvironment is possibly linked with a disruption in the NF-kB signalling pathway which may permit N. perurans to evade the host immune response. Finally it is proposed that an understanding of the mechanisms of localised immunosuppression will be particularly important for the development of new treatments for AGD since systemic immunostimulation may be ineffective without simultaneous disruption of the immune privilege-like microenvironment within AGD lesions.
Rights statementCopyright Copyright 2009 the Author Chapter 2 appears to be the equivalent of a post-print article published as: Young N. D., Crosbie P. B. B., Adams M. B., Nowak B. F. and Morrison R. N. (2007) Neoparamoeba perurans n. sp., an agent of amoebic gill disease of Atlantic salmon (Salmo salar L.). International Journal for Parasitology 37, 1469-1481, doi:10.1016/j.ijpara.2007.04.018 Chapter 3 appears to be the equivalent of a post-print article published as: Young N. D., Dykov‚àö¬8 I., Snekvik K., Nowak B. F. and Morrison R. N. (2008) Neoparamoeba perurans is a cosmopolitan aetiological agent of amoebic gill disease. Diseases of Aquatic Organisms 78, 217-223. doi:10.3354/dao01869 Chapter 5 appears to be the equivalent of the peer reviewed version of the following article: Young N. D., Dykov‚àö¬8 I., Nowak B. F. and Morrison R. N. (2008) Development of a diagnostic PCR to detect Neoparamoeba perurans, agent of amoebic gill disease (AGD). Journal of Fish Diseases 31, 285-295 which has been published in final form at DOI:10.1111/j.1365-2761.2008.00903.x This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Chapter 6 appears to be the equivalent of a post-print article published as: Young N. D., Cooper G. A., Nowak B. F., Koop B. F. and Morrison R. N. (2008) Coordinated down-regulation of the antigen processing machinery in the gills of amoebic gill disease-affected Atlantic salmon (Salmo salar L.). Molecular Immunology 45, 2581-2597. doi:10.1016/j.molimm.2007.12.023