Cross Talk Between Growth and Immunity: Coupling of the IGF Axis to Conserved Cytokine Pathways in Rainbow Trout

While disease and infection is associated with attenuated growth, the molecular pathways involved are poorly characterised. We postulated that the insulin-like growth factor (IGF) axis - a central governor of vertebrate growth - is repressed during infection to promote resource reallocation towards immunity. This 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 both IGF hormones, nineteen salmonid IGF binding proteins (IGFBPs) and a panel of marker genes for growth and immune status. There were major differences in the developmental response of the IGF axis to AS and VHSv, with the VHSv challenge causing strong downregulation of many genes. Despite this, IGFBP-1A1 and IGFBP-6A2 subtypes - each negative regulators of IGF signalling - were highly induced by AS and VHSv in striking correlation with host defence genes regulated by cytokine pathways. Follow up experiments demonstrated a highly-significant co-upregulation of IGFBP-1A1 and IGFBP-6A2 with proinflammatory cytokine genes in primary immune tissues (spleen and head kidney) when trout were challenged by a different Gram-negative 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 findings provide new and comprehensive insights into cross-talk between conserved pathways regulating teleost growth, development and immunity.