Polyinosinic:polycytidylic acid in vivo enhances Chinook salmon ( Oncorhynchus tshawytscha ) immunity and alters the fis

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Polyinosinic:polycytidylic acid in vivo enhances Chinook salmon (Oncorhynchus tshawytscha) immunity and alters the fish metabolome Ronald Lulijwa 1,2 & Andrea C. Alfaro 1 & Fabrice Merien 1,3 & Mark Burdass 4 & Jill Meyer 1,3 & Leonie Venter 1 & Tim Young 1,5 Received: 22 March 2020 / Accepted: 27 August 2020 / Published online: 25 September 2020 # Springer Nature Switzerland AG 2020

Abstract

Poly (I:C) is a viral pathogen-associated molecular pattern (PAMP) and a synthetic dsRNA analogue, which orchestrates antiviral responses through well conserved tolllike receptor 3 (tlr3), retinoic acid inducible gene I (RIG-1) like receptors (RLRs) and class A scavenger receptors (SR-As). This study investigated the effect of poly (I:C) in vivo on Chinook salmon (Oncorhynchus tshawytscha) haematology, innate immunity, serum and liver metabolite profiles, and lymphoid tissue cytokine transcript expression, over a 5-day period post-exposure. Poly (I:C) significantly enhanced differential monocyte and neutrophil counts, and reactive oxygen species (ROS) production in peripheral blood mononuclear cells (PBMCs). GC-MS-based metabolomics revealed that poly (I:C) significantly altered 23 liver and 13 serum metabolic features. Liver and serum metabolites involved in branched chain amino acid (BCAA) metabolism significantly increased at day 1 and returned to baseline by day 5; the citric acid cycle and ROS regulation were altered. Also, liver and serum metabolites involved in glycolysis were persistently depleted from day 1 to day 5. Liver metabolites involved in phospholipid metabolism increased at day 4 to 5 and decreased from day 2 to 4 in serum. At the molecular level, poly (I:C) upregulated antiviral ifnγ and Mx1, and anti-inflammatory il-10 in fish lymphoid tissues, which normalised to baseline by day 5. Overall, poly (I:C) induced innate and adaptive immune responses through multiple mechanisms and different levels in teleost O. tshawytscha. Findings may aid design and development of amelioration strategies against viral pathogens via metabolome reprograming. Targeted studies are recommended into identified pathways and survival biomarkers. Keywords Fish innate immunity . Metabolomics . Cytokine transcript expression . Poly (I:C)

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10499-02000599-w) contains supplementary material, which is available to authorized users.

* Andrea C. Alfaro [email protected] Extended author information available on the last page of the article

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Aquaculture International (2020) 28:2437–2463

Introduction The New Zealand aquaculture sector was valued at over US$ 820 million in 2017, of which Chinook salmon (Oncorhynchus tshawytscha) contributed 24% and 13% by value and production volume respectively (FAO 2019). New Zealand is the leading producer and supplier of farmed O. tshawytscha in the world. As the country’s aquaculture industry is founded on sustainable practices, O. tshawytscha production is considered to be “virus free” (Diggles 201

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