Growth and immunity cross-talk in rainbow trout: Suppression of the insulin-like growth factor system during infection

During disease and infection it is probable that growth is attenuated , the molecular pathways involved are poorly characterised. We postulated that the insulin - like growth factor (IGF) axis - a central endocrine governor of vertebrate growth - is repressed during infection to promote resource reallocation towards immunity. T his hypothesis was tested in rainbow trout ( Oncorhynchus mykiss ) challenged by Aeromonas salmonicida (AS), a Gram - negative bacterial pathogen, or viral hemorrhagic septicemia virus (VHSv) at hatch, first feeding and 3 weeks - post first - feeding. Quantitative transcriptional profiling was performed for genes encoding IGF hormones, all salmonid IGF - I receptor and IGF binding proteins , and a panel of marker genes for growth and immune status. Many IGF axis genes were developmentally upregulated in concert with g enes controlling muscle protein synthesis, recapturing the onset of complex growth regulation. There were also differences in the developmental response of the IGF axis to AS and VHSv, with the VHSv challenge causing strong downregulation of many genes. De spite this, IGFBP - 1A1 and IGFBP - 6A2 subtypes - each negative regulators of IGF signalling - were massively induced by AS and VHSv in striking correlation with host defence genes regulated by cytokine pathways. Follow up experiments demonstrated a massive u pregulation of IGFBP - 1A1 , IGFBP - 6A2 and proinflammatory cytokine genes , associated with large downregulation of genes encoding IGF hormones and IGF - I receptor in spleen and head kidney of rainbow trout challenged by a different bacterium, Yersinia ruckeri . Based on our findings, we propose a model where certain IGFBP subtypes are directly regulated by cytokine signalling pathways, allowing immediate modulation of growth and/or immune system phenotypes according to the level of activation of immunity. Our fi ndings provide new and comprehensive insights into cross - talk between conserved pathways regulating teleost growth, development and immunity