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

Poly (I:C) is a viral pathogen-associated molecular pattern (PAMP) and a synthetic dsRNA analogue, which orchestrates antiviral responses through well conserved toll-like 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.